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Sample records for acting neuromuscular blocking

  1. Neuromuscular block

    PubMed Central

    Bowman, W C

    2006-01-01

    Descriptions of the South American arrow poisons known as curares were reported by explorers in the 16th century, and their site of action in producing neuromuscular block was determined by Claude Bernard in the mid-19th century. Tubocurarine, the most important curare alkaloid, played a large part in experiments to determine the role of acetylcholine in neuromuscular transmission, but it was not until after 1943 that neuromuscular blocking drugs became established as muscle relaxants for use during surgical anaesthesia. Tubocurarine causes a number of unwanted effects, and there have been many attempts to replace it. The available drugs fall into two main categories: the depolarising blocking drugs and the nondepolarising blocking drugs. The former act by complex mixed actions and are now obsolete with the exception of suxamethonium, the rapid onset and brief duration of action of which remain useful for intubation at the start of surgical anaesthesia. The nondepolarising blocking drugs are reversible acetylcholine receptor antagonists. The main ones are the atracurium group, which possess a built-in self-destruct mechanism that makes them especially useful in kidney or liver failure, and the vecuronium group, which are especially free from unwanted side effects. Of this latter group, the compound rocuronium is of especial interest because its rapid onset of action allows it to be used for intubation, and there is promise that its duration of action may be rapidly terminated by a novel antagonist, a particular cyclodextrin, that chelates the drug, thereby removing it from the acetylcholine receptors. PMID:16402115

  2. Anaphylactic reactions during anaesthesia: neuromuscular blocking agents, latex and antibiotics.

    PubMed

    2013-05-01

    A French team investigated hypersensitivity reactions that occurred during locoregional or general anaesthesia over an 8-year period. They estimated that the incidence of anaphylactic reactions was about 1 per 10 000 anaesthetic procedures. Among the 1816 reports of anaphylactic reactions, the most commonly implicated drugs were neuromuscular blocking agents (1067 cases), latex (361 cases), and antibiotics (236 cases). Some anaphylactic reactions to neuromuscular blocking agents occurred in patients who had never previously been anaesthetised, suggesting cross-reactivity with other, poorly known, substances. Most reactions in children were due to latex, followed by neuromuscular blocking agents and antibiotics. In practice, exposure to latex devices should be minimised, or simply avoided when possible. A history of sensitization to substances sharing allergenic sites with neuromuscular blocking agents should be investigated, and measures should be taken to protect patients.

  3. Train-of-four fade during onset of neuromuscular block with nondepolarising neuromuscular blocking agents.

    PubMed

    Gibson, F M; Mirakhur, R K

    1989-04-01

    Fade in the train-of-four (TOF) responses during onset of neuromuscular block was studied following administration of atracurium (225 or 450 micrograms/kg), vecuronium (40 or 80 micrograms/kg), pancuronium (60 or 120 micrograms/kg) and tubocurarine (450 micrograms/kg). TOF ratios were measured at approximate heights of T1 (first response in the TOF) of 75, 50 and 25%. Fade in TOF increased as the height of T1 decreased, with maximum fade being observed at T1 of 25%. The greatest difference between relaxants was observed at T1 of 25%, vecuronium showing the least fade and pancuronium, atracurium and tubocurarine showing increasing fade, in that order. The difference between atracurium and tubocurarine or between vecuronium and pancuronium was not significant, but the degree of TOF fade was significantly greater with atracurium and tubocurarine in comparison to vecuronium or pancuronium.

  4. Neuromuscular block after intra-arterially injected acetylcholine

    PubMed Central

    Pinelli, P.; Tonali, P.; Gambi, D.

    1973-01-01

    It has been suggested that the effect of ACTH in myasthenia gravis may be ascribed to an action involving neuromuscular transmission which favours repolarization processes, with a tendency towards hyperpolarization of the membranes of muscle fibres and motor nerve endings. A similar mechanism has been postulated for the action of ACTH in epilepsy (Klein, 1970). A direct or indirect action on nerve membrane would interfere with depolarization. There is evidence of raised concentration of intracellular potassium and increased outflow of sodium ions which would cause hyperpolarization of the membrane. This paper studies the effect of ACTH on the late block of neuromuscular transmission caused by acetylcholine (ACTH). Images PMID:4350704

  5. Neuromuscular block after intra-arterially injected acetylcholine

    PubMed Central

    Tonali, P.; Gambi, D.

    1973-01-01

    The neuromuscular depolarizing block induced by intra-arterially injected ACh was studied to determine the variability in the same subject and in different subjects without disorders at the motor end-plate. Amplitude of action potentials of the opponens pollicis muscle evoked by intermittent repetitive supramaximal stimulation of the median nerve at the wrist were recorded for one hour from the beginning of ACh injection. The features of prompt and late depression stages after the injection were analysed statistically. Re-testing of the same subjects after a while shows that, in spite of all efforts to maintain the same experimental conditions, variations do occur in late depression. Time course and duration are particularly affected, while the degree of depression is altered but slightly. The presence of such variations limits this test to evaluation of the influence of other factors only within their already established statistical limits. Images PMID:4350703

  6. Tetanic fade following administration of nondepolarizing neuromuscular blocking drugs.

    PubMed

    Gibson, F M; Mirakhur, R K

    1989-06-01

    Fade in response to tetanic stimulation was studied following administration of atracurium 120 or 225 micrograms/kg, vecuronium 23 or 40 micrograms/kg, pancuronium 30 or 60 micrograms/kg, or d-tubocurarine 185 or 450 micrograms/kg. Ten patients received each dose and tetanic fade was measured at maximum block in the patients, who received the lower doses of the relaxants or at 10% recovery in those who received the higher doses. Fade during tetanic stimulation was generally similar in all the groups with the exception of the higher dose of pancuronium which showed a significantly greater fade in comparison with the higher doses of atracurium and d-tubocurarine. If fade in response to tetanic stimulation represents a prejunctional effect, the results from the present study suggest that neuromuscular blocking drugs cannot be differentiated with respect to their relative prejunctional effects by measurement of tetanic fade during established block after administration of clinically useful doses as used in the present study.

  7. Are neuromuscular blocking agents being misused in laboratory pigs?

    PubMed

    Bradbury, A G; Clutton, R E

    2016-04-01

    The literature (2012-4) describing experimental pig surgery was reviewed to estimate the extent to which neuromuscular block (NMB) is used, to examine methods for ensuring unconsciousness, and to identify the rationale for use of NMB and establish the anaesthetist's training. In the first stage of a two-stage review, NMB use was estimated using Web of Knowledge to identify articles describing NMB during pig surgeries. In the second stage, PubMed and Google Scholar were used to increase the number of articles for determining measures taken to prevent accidental awareness during general anaesthesia (AAGA). The corresponding authors of screened articles were emailed four times to establish the reason for using NMB and the anaesthetists' backgrounds (medical, veterinary, or technical). The first search revealed NMB use in 80 of 411 (20%) studies. Of the 153 articles analysed in the second stage, two described strategies to reduce AAGA. Some (6%) papers did not provide information on anaesthetic doses; citations supporting anaesthetic efficacy were found in only 13. Five of 69 papers using inhalation agents measured end-tidal anaesthetic concentrations based on human, not porcine, minimal alveolar concentrations. The methods in 13% of articles reporting anaesthetic depth assessment were incomplete or questionable, or both; four described using somatic motor reflexes. Corresponding authors of 121 articles reported that the principal reason for NMB was improved 'surgical visualization' (26%). Medical or veterinary anaesthetists supervised anaesthesia in 70% of studies; non-anaesthetists provided NMB, unsupervised, in 23. Nine respondents prioritized experimental expediency over pig welfare. In laboratory pig studies, AAGA may be prevalent; reported details of its attempted prevention are woefully inadequate.

  8. [Prolonged neuromuscular block induced by mivacurium in a patient treated with cyclophosphamide].

    PubMed

    Vigouroux, D; Voltaire, L

    1995-01-01

    A case is reported of prolonged neuromuscular block after mivacurium chloride for laparoscopic cholecystectomy, in a 45 years old patient, treated with cyclophosphamide for a Wegener's granulomatosis. The neuromuscular function monitoring by train-of-four showed a duration of action of 75 min after an intubation dose of 0.20 mg.kg-1. Additional bolus of 1 mg, corresponding to 25% of usual doses, every 10 or 15 min, were sufficient for maintaining muscle relaxation. Spontaneous recovery, without any antagonization, lasted 40 min for a TOF ratio (T4/T1) > or = 70%. Recovery index from 25 to 75% were 13 min. Plasma butyrilcholinesterases activity were reduced to a level of 50%. With reference to literature about succinylcholine, the responsibility of cyclophosphamide is likely, and discussed. This observation shows the value of monitoring the neuromuscular transmission. PMID:8745976

  9. Preferences of Mexican anesthesiologists for vecuronium, rocuronium, or other neuromuscular blocking agents: a survey

    PubMed Central

    Nava-Ocampo, A A; Ramírez-Mora, J C; Moyao-García, D; Garduño-Espinosa, J; Salmerón, J

    2002-01-01

    Background Several neuromuscular blocking (NMB) agents are available for clinical use in anesthesia. The present study was performed in order to identify preferences and behaviors of anesthesiologists for using vecuronium, rocuronium or other NMB agents in their clinical practice. Material and methods The cross-sectional survey was applied at the Updated Course of the Colegio Mexicano de Anestesiología performed last year. Of 989, 282 (28.5%) surveys were returned. Results Most anesthesiologists were working at both public and private hospitals, performed anesthetic procedures for hospitalized and ambulatory patients, and anesthetized children as well as adults. Respondents did not consider mechanomyography as the gold standard method for neuromuscular monitoring. The T25 was not recognized as a pharmacodynamic parameter that represents the clinical duration of the neuromuscular block. Most answered that vecuronium induces less histamine release than rocuronium, had never used any neuromuscular monitor, did not know the cost of vecuronium and rocuronium, and preferred rocuronium in multiple-sampling vials and vecuronium in either a vial for single or multiple sampling. Rocuronium was preferred for emergency surgery in patients with full stomach only. Almost all of anesthesiologists that conserve the unused drug did it without refrigeration and more than 30% conserve the unused drug in one syringe for further use. Conclusion Vecuronium was preferred for most clinical situations, and the decision for this choice was not based on costs. Storage of unused drugs without refrigeration in a single syringe for purpose of future use in several patients represented a dangerous common practice. PMID:11991809

  10. Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine.

    PubMed Central

    2010-01-01

    Background Acetylcholinesterase inhibitors cannot rapidly reverse profound neuromuscular block. Sugammadex, a selective relaxant binding agent, reverses the effects of rocuronium and vecuronium by encapsulation. This study assessed the efficacy of sugammadex compared with neostigmine in reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia. Methods Patients aged ≥18 years, American Society of Anesthesiologists class 1-4, scheduled to undergo surgery under general anesthesia were enrolled in this phase III, multicenter, randomized, safety-assessor blinded study. Sevoflurane anesthetized patients received vecuronium 0.1 mg/kg for intubation, with maintenance doses of 0.015 mg/kg as required. Patients were randomized to receive sugammadex 4 mg/kg or neostigmine 70 μg/kg with glycopyrrolate 14 μg/kg at 1-2 post-tetanic counts. The primary efficacy variable was time from start of study drug administration to recovery of the train-of-four ratio to 0.9. Safety assessments included physical examination, laboratory data, vital signs, and adverse events. Results Eighty three patients were included in the intent-to-treat population (sugammadex, n = 47; neostigmine, n = 36). Geometric mean time to recovery of the train-of-four ratio to 0.9 was 15-fold faster with sugammadex (4.5 minutes) compared with neostigmine (66.2 minutes; p < 0.0001) (median, 3.3 minutes with sugammadex versus 49.9 minutes with neostigmine). No serious drug-related adverse events occurred in either group. Conclusions Recovery from profound vecuronium-induced block is significantly faster with sugammadex, compared with neostigmine. Neostigmine did not rapidly reverse profound neuromuscular block (Trial registration number: NCT00473694). PMID:20809967

  11. Magnesium-induced recurarisation after reversal of rocuronium-induced neuromuscular block with sugammadex.

    PubMed

    Unterbuchner, C; Ziegleder, R; Graf, B; Metterlein, T

    2015-04-01

    A 61-year-old woman (57 kg, 171 cm) underwent surgery under general anaesthesia with desflurane 5.8-6.1 vol. % end-tidal, remifentanil 0.2-0.4 μg/kg/min and rocuronium 35 mg (0.61 mg/kg). On return of the second twitch in the train-of-four (TOF) stimulation measured by acceleromyography, sugammadex 120 mg (2.1 mg/kg) was given. After complete neuromuscular recovery, magnesium sulphate 3600 mg (60 mg/kg) was injected intravenously over 5 min to treat atrial fibrillation. This was associated with recurarisation with a nadir [first twitch=25%, TOF ratio (TOFR)=67%] 7 min after the start of the magnesium sulphate infusion (magnesium plasma level: 2.67 mM). A spontaneous twitch value and a TOFR of >90% were observed 45 min after the beginning of the magnesium sulphate infusion under general anaesthesia. Rapid infusion of magnesium sulphate may re-establish a sugammadex-reversed, rocuronium-induced neuromuscular block during general anaesthesia, probably because of the high plasma level of magnesium (2.67 mM). Desflurane and a small fraction of unbound rocuronium may amplify the known muscle relaxing effects of magnesium. Intravenous injection of magnesium sulphate is not recommended in patients after general anaesthesia with neuromuscular relaxants, particularly after sugammadex reversal. Quantitative neuromuscular monitoring should be used for reversing aminosteroid muscle relaxants with sugammadex--particularly in combination with magnesium injection--to prevent post-operative residual curarisation.

  12. The neuromuscular blocking properties of a series of bis-quaternary tropeïnes

    PubMed Central

    Haining, C. G.; Johnston, R. G.; Smith, J. M.

    1960-01-01

    Linkage of two tropine esters through their nitrogen atoms by the chain -[CH2]m-O-CO-[CH2]n-CO-O-[CH2]m-, in which m was 2 or 3 and n varied from 0 to 6, gave compounds which produced neuromuscular block without depolarization. Reversibility be neostigmine was confirmed for a few compounds. Potency was found to depend upon the tropine ester employed and upon the values of n and m. Short duration and hypotensive properties were favoured by the higher values of n. The duration of action of the compound based on the phenylacetic acid ester of tropine, in which n=4 and m=2, varied considerably in different species. Epimerization, in which the relative positions of the methyl group and the linking chain on the quaternary tropane nitrogen atom were reversed, did not produce subtances having more favourable properties than those possessed by the unepimerized compounds. PMID:14398886

  13. Neuromuscular dysfunction with the experimental arm acting as its own reference following eccentric and isometric exercise.

    PubMed

    Philippou, Anastassios; Bogdanis, Gregory C; Maridaki, Maria

    2010-01-01

    Eccentric exercise has been extensively used as a model to study muscle damage-induced neuromuscular impairment, adopting mainly a bilateral matching task between the reference (unexercised) arm and the indicator (exercised) arm. However, little attention has been given to the muscle proprioceptive function when the exercised arm acts as its own reference. This study investigated muscle proprioception and motor control, with the arm acting both as reference and indicator, following eccentric exercise and compared them with those observed after isometric exercise. Fourteen young male volunteers were equally divided into two groups and performed an eccentric or isometric exercise protocol with the elbow flexors of the non-dominant arm on an isokinetic dynamometer. Both exercise protocols induced significant changes in indicators of muscle damage, that is, muscle soreness, range of motion and maximal isometric force post-exercise (p < 0.05-0.001), and neuromuscular function was similarly affected following both protocols. Perception of force was impaired over the 4-day post-exercise period (p < 0.001), with the applied force being systematically overestimated. Perception of joint position was significantly disturbed (i.e., target angle was underestimated) only at one elbow angle on day 4 post-exercise (p < 0.05). The misjudgements and disturbed motor output observed when the exercised arm acted as its own reference concur with the view that they could be a result of a mismatch between the central motor command and an impaired motor control after muscle damage. PMID:20553224

  14. Exploring the link between pholcodine exposure and neuromuscular blocking agent anaphylaxis

    PubMed Central

    Brusch, Anna M; Clarke, Russell C; Platt, Peter R; Phillips, Elizabeth J

    2014-01-01

    Neuromuscular blocking agents (NMBAs) are the most commonly implicated drugs in IgE-mediated anaphylaxis during anaesthesia that can lead to perioperative morbidity and mortality. The rate of NMBA anaphylaxis shows marked geographical variation in patients who have had no known prior exposure to NMBAs, suggesting that there may be external or environmental factors that contribute to the underlying aetiology and pathophysiology of reactions. Substituted ammonium ions are shared among NMBAs and are therefore thought to be the main allergenic determinant of this class of drugs. Substituted ammonium ions are found in a wide variety of chemical structures, including prescription medications, over-the-counter medications and common household chemicals, such as the quaternary ammonium disinfectants. Epidemiological studies have shown parallels in the consumption of pholcodine, a nonprescription antitussive drug which contains a tertiary ammonium ion, and the incidence of NMBA anaphylaxis. This link has prompted the withdrawal of pholcodine in some countries, with an ensuing fall in the observed rate of NMBA anaphylaxis. While such observations are compelling in their suggestion of a relationship between pholcodine exposure and NMBA hypersensitivity, important questions remain regarding the mechanisms by which pholcodine is able to sensitize against NMBAs and whether there are other, as yet unidentified, agents that can elicit similar hypersensitivity reactions. This review aims to explore the evidence linking pholcodine exposure to NMBA hypersensitivity and discuss the implications for our understanding of the pathophysiology of these reactions. PMID:24251966

  15. Exploring the link between pholcodine exposure and neuromuscular blocking agent anaphylaxis.

    PubMed

    Brusch, Anna M; Clarke, Russell C; Platt, Peter R; Phillips, Elizabeth J

    2014-07-01

    Neuromuscular blocking agents (NMBAs) are the most commonly implicated drugs in IgE-mediated anaphylaxis during anaesthesia that can lead to perioperative morbidity and mortality. The rate of NMBA anaphylaxis shows marked geographical variation in patients who have had no known prior exposure to NMBAs, suggesting that there may be external or environmental factors that contribute to the underlying aetiology and pathophysiology of reactions. Substituted ammonium ions are shared among NMBAs and are therefore thought to be the main allergenic determinant of this class of drugs. Substituted ammonium ions are found in a wide variety of chemical structures, including prescription medications, over-the-counter medications and common household chemicals, such as the quaternary ammonium disinfectants. Epidemiological studies have shown parallels in the consumption of pholcodine, a nonprescription antitussive drug which contains a tertiary ammonium ion, and the incidence of NMBA anaphylaxis. This link has prompted the withdrawal of pholcodine in some countries, with an ensuing fall in the observed rate of NMBA anaphylaxis. While such observations are compelling in their suggestion of a relationship between pholcodine exposure and NMBA hypersensitivity, important questions remain regarding the mechanisms by which pholcodine is able to sensitize against NMBAs and whether there are other, as yet unidentified, agents that can elicit similar hypersensitivity reactions. This review aims to explore the evidence linking pholcodine exposure to NMBA hypersensitivity and discuss the implications for our understanding of the pathophysiology of these reactions. PMID:24251966

  16. Self-learning fuzzy control with temporal knowledge for atracurium-induced neuromuscular block during surgery.

    PubMed

    Mason, D G; Ross, J J; Edwards, N D; Linkens, D A; Reilly, C S

    1999-06-01

    Self-learning fuzzy logic control has the important property of accommodating uncertain, nonlinear, and time-varying process characteristics. This intelligent control scheme starts with no fuzzy control rules and learns how to control each process presented to it in real time without the need for detailed process modeling. In this study we utilize temporal knowledge of generated rules to improve control performance. A suitable medical application to investigate this control strategy is atracurium-induced neuromuscular block of patients in the operating theater where the patient response exhibits high nonlinearity and individual patient dose requirements may vary fivefold during an operating procedure. We developed a computer control system utilizing Relaxograph (Datex) measurements to assess the clinical performance of a self-learning fuzzy controller in this application. Using a T1 setpoint of 10% of baseline in 10 patients undergoing general surgery, we found a mean T1 error of 0.28% (SD = 0.39%) while accommodating a 0.25 to 0.38 mg/kg/h range in the mean atracurium infusion rate. This result compares favorably with more complex and computationally intensive model-based control strategies for atracurium infusion. PMID:10356301

  17. Atracurium Besylate and other neuromuscular blocking agents promote astroglial differentiation and deplete glioblastoma stem cells

    PubMed Central

    Spina, Raffaella; Voss, Dillon M.; Asnaghi, Laura; Sloan, Andrew; Bar, Eli E.

    2016-01-01

    Glioblastoma multiforme (GBM) are the most common primary malignant brain tumor in adults, with a median survival of about one year. This poor prognosis is attributed primarily to therapeutic resistance and tumor recurrence after surgical removal, with the root cause suggested to be found in glioblastoma stem cells (GSCs). Using glial fibrillary acidic protein (GFAP) as a reporter of astrocytic differentiation, we isolated multiple clones from three independent GSC lines which express GFAP in a remarkably stable fashion. We next show that elevated expression of GFAP is associated with reduced clonogenicity in vitro and tumorigenicity in vivo. Utilizing this in vitro cell-based differentiation reporter system we screened chemical libraries and identified the non-depolarizing neuromuscular blocker (NNMB), Atracurium Besylate, as a small molecule which effectively induces astroglial but not neuronal differentiation of GSCs. Functionally, Atracurium Besylate treatment significantly inhibited the clonogenic capacity of several independent patient-derived GSC neurosphere lines, a phenomenon which was largely irreversible. A second NNMB, Vecuronium, also induced GSC astrocytic differentiation while Dimethylphenylpiperazinium (DMPP), a nicotinic acetylcholine receptor (nAChR) agonist, significantly blocked Atracurium Besylate pro-differentiation activity. To investigate the clinical importance of nAChRs in gliomas, we examined clinical outcomes and found that glioma patients with tumors overexpressing CHRNA1 or CHRNA9 (encoding for the AChR-α1 or AChR-α9) exhibit significant shorter overall survival. Finally, we found that ex-vivo pre-treatment of GSCs, expressing CHRNA1 and CHRNA9, with Atracurium Besylate significantly increased the survival of mice xenotransplanted with these cells, therefore suggesting that tumor initiating subpopulations have been reduced. PMID:26575950

  18. Lesions of rat skeletal muscle after local block of acetylcholinesterase and neuromuscular stimulation.

    PubMed

    Mense, S; Simons, D G; Hoheisel, U; Quenzer, B

    2003-06-01

    In skeletal muscle, a local increase of acetylcholine (ACh) in a few end plates has been hypothesized to cause the formation of contraction knots that can be found in myofascial trigger points. To test this hypothesis in rats, small amounts of an acetylcholinesterase inhibitor [diisopropylfluorophosphate (DFP)] were injected into the proximal half of the gastrocnemius muscle, and the muscle nerve was electrically stimulated for 30-60 min for induction of muscle twitches. The distal half of the muscle, which performed the same contractions, served as a control to assess the effects of the twitches without DFP. Sections of the muscle were evaluated for morphological changes in relation to the location of blocked end plates. Compared with the distal half of the muscle, the DFP-injected proximal half exhibited significantly higher numbers of abnormally contracted fibers (local contractures), torn fibers, and longitudinal stripes. DFP-injected animals in which the muscle nerve was not stimulated and that were allowed to survive for 24 h exhibited the same lesions but in smaller numbers. The data indicate that an increased concentration of ACh in a few end plates causes damage to muscle fibers. The results support the assumption that a dysfunctional end plate exhibiting increased release of ACh may be the starting point for regional abnormal contractions, which are thought to be essential for the formation of myofascial trigger points.

  19. Anaesthetic Tricaine Acts Preferentially on Neural Voltage-Gated Sodium Channels and Fails to Block Directly Evoked Muscle Contraction

    PubMed Central

    Attili, Seetharamaiah; Hughes, Simon M.

    2014-01-01

    Movements in animals arise through concerted action of neurons and skeletal muscle. General anaesthetics prevent movement and cause loss of consciousness by blocking neural function. Anaesthetics of the amino amide-class are thought to act by blockade of voltage-gated sodium channels. In fish, the commonly used anaesthetic tricaine methanesulphonate, also known as 3-aminobenzoic acid ethyl ester, metacaine or MS-222, causes loss of consciousness. However, its role in blocking action potentials in distinct excitable cells is unclear, raising the possibility that tricaine could act as a neuromuscular blocking agent directly causing paralysis. Here we use evoked electrical stimulation to show that tricaine efficiently blocks neural action potentials, but does not prevent directly evoked muscle contraction. Nifedipine-sensitive L-type Cav channels affecting movement are also primarily neural, suggesting that muscle Nav channels are relatively insensitive to tricaine. These findings show that tricaine used at standard concentrations in zebrafish larvae does not paralyse muscle, thereby diminishing concern that a direct action on muscle could mask a lack of general anaesthesia. PMID:25090007

  20. Static balance and function in children with cerebral palsy submitted to neuromuscular block and neuromuscular electrical stimulation: Study protocol for prospective, randomized, controlled trial

    PubMed Central

    2012-01-01

    Background The use of botulinum toxin A (BT-A) for the treatment of lower limb spasticity is common in children with cerebral palsy (CP). Following the administration of BT-A, physical therapy plays a fundamental role in potentiating the functionality of the child. The balance deficit found in children with CP is mainly caused by muscle imbalance (spastic agonist and weak antagonist). Neuromuscular electrical stimulation (NMES) is a promising therapeutic modality for muscle strengthening in this population. The aim of the present study is to describe a protocol for a study aimed at analyzing the effects of NMES on dorsiflexors combined with physical therapy on static and functional balance in children with CP submitted to BT- A. Methods/Design Protocol for a prospective, randomized, controlled trial with a blinded evaluator. Eligible participants will be children with cerebral palsy (Levels I, II and III of the Gross Motor Function Classification System) between five and 12 years of age, with independent gait with or without a gait-assistance device. All participants will receive BT-A in the lower limbs (triceps surae). The children will then be randomly allocated for either treatment with motor physical therapy combined with NMES on the tibialis anterior or motor physical therapy alone. The participants will be evaluated on three occasions: 1) one week prior to the administration of BT-A; 2) one week after the administration of BT-A; and 3) four months after the administration of BT-A (end of intervention). Spasticity will be assessed by the Modified Ashworth Scale and Modified Tardieu Scale. Static balance will be assessed using the Medicapteurs Fusyo pressure platform and functional balance will be assessed using the Berg Balance Scale. Discussion The aim of this protocol study is to describe the methodology of a randomized, controlled, clinical trial comparing the effect of motor physical therapy combined with NMES on the tibialis anterior muscle or motor

  1. Neuromuscular Disorders

    MedlinePlus

    Neuromuscular disorders affect the nerves that control your voluntary muscles. Voluntary muscles are the ones you can control, like ... and your ability to breathe. Examples of neuromuscular disorders include Amyotrophic lateral sclerosis Multiple sclerosis Myasthenia gravis ...

  2. Detection of attempted movement from the EEG during neuromuscular block: proof of principle study in awake volunteers

    PubMed Central

    Blokland, Yvonne; Spyrou, Loukianos; Lerou, Jos; Mourisse, Jo; Jan Scheffer, Gert; Geffen, Geert-Jan van; Farquhar, Jason; Bruhn, Jörgen

    2015-01-01

    Brain-Computer Interfaces (BCIs) have the potential to detect intraoperative awareness during general anaesthesia. Traditionally, BCI research is aimed at establishing or improving communication and control for patients with permanent paralysis. Patients experiencing intraoperative awareness also lack the means to communicate after administration of a neuromuscular blocker, but may attempt to move. This study evaluates the principle of detecting attempted movements from the electroencephalogram (EEG) during local temporary neuromuscular blockade. EEG was obtained from four healthy volunteers making 3-second hand movements, both before and after local administration of rocuronium in one isolated forearm. Using offline classification analysis we investigated whether the attempted movements the participants made during paralysis could be distinguished from the periods when they did not move or attempt to move. Attempted movement trials were correctly identified in 81 (68–94)% (mean (95% CI)) and 84 (74–93)% of the cases using 30 and 9 EEG channels, respectively. Similar accuracies were obtained when training the classifier on the participants’ actual movements. These results provide proof of the principle that a BCI can detect movement attempts during neuromuscular blockade. Based on this, in the future a BCI may serve as a communication channel between a patient under general anaesthesia and the anaesthesiologist. PMID:26248679

  3. The effect of centrophenoxine at the skeletal neuromuscular junction.

    PubMed

    Mistry, S D; Tripathi, C G; Bhavsar, V H; Kelkar, V V

    1985-01-01

    Centrophenoxine exhibited some interesting actions at the neuromuscular junction. The drug was ineffective in rat or chick preparations, but blocked neuromuscular transmission in frog preparations. The blockade was reversed by adrenaline, potassium, choline and physostigmine. The drug had no effect on muscle contractility or endplate cholinoceptor. Hemicholinium 3 induced a neuromuscular blockade in rat (in vivo) which was reversed by choline but not by centrophenoxine. Neither of these two drugs could reverse the blocking effect of hemicholinium in frog preparations. It is concluded that centrophenoxine acts only in frog and the blockade involves a presynaptic mechanism. The work further suggests that choline uptake systems in the rat and the frog may not be identical, since choline competed with hemicholinium for the uptake system in rat and with centrophenoxine (but not with hemicholinium) in the frog.

  4. Neuromuscular blockade: what was, is and will be.

    PubMed

    Schepens, Tom; Cammu, Guy

    2014-01-01

    Non-depolarizing neuromuscular blocking agents (NMBAs) produce neuromuscular blockade by competing with acetylcholine at the neuromuscular junction, whereas depolarizing NMBAs open receptor channels in a manner similar to that of acetylcholine. Problems with NMBAs include malignant hyperthermia caused by succinylcholine, anaphylaxis with the highest incidence for succinylcholine and rocuronium, and residual neuromuscular blockade. To reverse these blocks, anticholinesterases can act indirectly by increasing the amount of acetylcholine in the neuromuscular junction; sugammadex is the only selective relaxant binding agent (SRBA) in clinical use. At all levels of blockade, recovery after sugammadex is faster than after neostigmine. Sugammadex potentially also has some other advantages over neostigmine that are related to neostigmine's increase in the amount of acetylcholine and the necessity of co-administering anticholinergics. However, hypersensitivity reactions, including anaphylaxis, have occurred in some patients and healthy volunteers after sugammadex and remain an issue for the FDA. In the near future, we may see the emergence of new SRBAs and of easier-to-use technologies that can routinely monitor neuromuscular transmissions in daily practice. The nature of the effect of sugammadex on freeing nicotinic acetylcholine receptors located outside the neuromuscular junction from NMBAs is unknown. Moreover, it is uncertain whether the full removal of the competing antagonists (by SRBAs) at the neuromuscular junction impacts the efficiency of acetylcholine transmission. In a recent pilot study in healthy volunteers, we demonstrated increased electromyographic diaphragm activity after sugammadex, compared to neostigmine. Further research is needed to elucidate the role of NMBAs and their reversal agents in the central control of breathing, respiratory muscle activity, and respiratory outcomes. PMID:25622380

  5. Neuromuscular Scoliosis

    MedlinePlus

    ... degree of neuromuscular involvement. Diagnosis Incidence of Scoliosis Cerebral palsy (2 limbs involved) 25% Myelodysplasia (lower lumbar) 60% Spinal muscle atrophy 67% Friedreich ataxia 80% Cerebral palsy (4 limbs involved) 80% Duchenne muscular dystrophy 90% ...

  6. In Vitro selectivity of an acyclic cucurbit[n]uril molecular container towards neuromuscular blocking agents relative to commonly used drugs.

    PubMed

    Ganapati, Shweta; Zavalij, Peter Y; Eikermann, Matthias; Isaacs, Lyle

    2016-01-28

    An acyclic cucurbit[n]uril (CB[n]) based molecular container (2, a.k.a. Calabadion 2) binds to both amino-steroidal and benzylisoquinolinium type neuromuscular blocking agents (NMBAs) in vitro, and reverses the effect of these drugs in vivo displaying faster recovery times than placebo and the γ-cyclodextrin (CD) based and clinically used reversal agent Sugammadex. In this study we have assessed the potential for other drugs commonly used during and after surgery (e.g. antibiotics, antihistamines, and antiarrhythmics) to interfere with the ability of 2 to bind NMBAs rocuronium and cisatracurium in vitro. We measured the binding affinities (Ka, M(-1)) of twenty seven commonly used drugs towards 2 and simulated the equilibrium between 2, NMBA, and drug based on their standard clinical dosages to calculate the equilibrium concentration of 2·NMBA in the presence of the various drugs. We found that none of the 27 drugs studied possess the combination of a high enough binding affinity with 2 and a high enough standard dosage to be able to promote the competitive dissociation (a.k.a. displacement interactions) of the 2·NMBA complex with the formation of the 2·drug complex. Finally, we used the simulations to explore how the potential for displacement interactions is affected by a number of factors including the Ka of the 2·NMBA complex, the Ka of the AChR·NMBA complex, the Ka of the 2·drug complex, and the dosage of the drug. PMID:26648135

  7. In Vitro selectivity of an acyclic cucurbit[n]uril molecular container towards neuromuscular blocking agents relative to commonly used drugs.

    PubMed

    Ganapati, Shweta; Zavalij, Peter Y; Eikermann, Matthias; Isaacs, Lyle

    2016-01-28

    An acyclic cucurbit[n]uril (CB[n]) based molecular container (2, a.k.a. Calabadion 2) binds to both amino-steroidal and benzylisoquinolinium type neuromuscular blocking agents (NMBAs) in vitro, and reverses the effect of these drugs in vivo displaying faster recovery times than placebo and the γ-cyclodextrin (CD) based and clinically used reversal agent Sugammadex. In this study we have assessed the potential for other drugs commonly used during and after surgery (e.g. antibiotics, antihistamines, and antiarrhythmics) to interfere with the ability of 2 to bind NMBAs rocuronium and cisatracurium in vitro. We measured the binding affinities (Ka, M(-1)) of twenty seven commonly used drugs towards 2 and simulated the equilibrium between 2, NMBA, and drug based on their standard clinical dosages to calculate the equilibrium concentration of 2·NMBA in the presence of the various drugs. We found that none of the 27 drugs studied possess the combination of a high enough binding affinity with 2 and a high enough standard dosage to be able to promote the competitive dissociation (a.k.a. displacement interactions) of the 2·NMBA complex with the formation of the 2·drug complex. Finally, we used the simulations to explore how the potential for displacement interactions is affected by a number of factors including the Ka of the 2·NMBA complex, the Ka of the AChR·NMBA complex, the Ka of the 2·drug complex, and the dosage of the drug.

  8. In patients with head injuries who undergo rapid sequence intubation using succinylcholine, does pretreatment with a competitive neuromuscular blocking agent improve outcome? A literature review

    PubMed Central

    Clancy, M; Halford, S; Walls, R; Murphy, M

    2001-01-01

    A literature search was undertaken for evidence of the effect of succinylcholine (SCH) on the intracranial pressure (ICP) of patients with acute brain injury and whether pretreatment with a defasciculating dose of competitive neuromuscular blocker is beneficial in this patient group. The authors could find no definitive evidence that SCH caused a rise in ICP in patients with brain injury. However, these studies were often weak and small. For those patients suffering acute traumatic brain injury the authors could find no studies that investigated the issue of pretreatment with defasciculating doses of competitive neuromuscular blockers and their effect on ICP in patients given SCH. There is level 2 evidence that SCH caused an increase in ICP for patients undergoing neurosurgery for brain tumours with elective anaesthesia and that pretreatment with defasciculating doses of neuromuscular blockers reduced such increases. It is unknown if this affects neurological outcome for this patient group. PMID:11559609

  9. Dollars and Sense: Diverse Perspectives on Block Grants and the Personal Responsibility Act.

    ERIC Educational Resources Information Center

    Gardner, Sid; And Others

    In March 1995, the U.S. House of Representatives passed the Personal Responsibility Act (H.R. 4), part of the House Republican Contract with America. The bill would move primary responsibility for child and family programs to states and communities, reduce federal spending, and consolidate programs into block grants for child care, child…

  10. 48 CFR 52.250-3 - SAFETY Act Block Designation/Certification.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... review are based on the factors identified in 6 CFR 25.4(b). (e) Neither SAFETY Act designation nor..., injury or other loss to citizens or institutions of the United States. Block certification means SAFETY... issued. For purposes of defining a QATT, technology means any product, equipment, service...

  11. Neuromuscular Blockade and Reversal Agents: A Primer for Postanesthesia Nurses.

    ERIC Educational Resources Information Center

    Pesci, Barbara R.

    1986-01-01

    Presents a comprehensive review of neuromuscular blocking agents, reversal agents used in anesthesia, and factors affecting reversal. It is aimed at nurses who provide care to patients recovering from anesthesia. It discusses the neuromuscular transmission system, depolarizing muscle relaxants, nondepolarizing blocking agents, and criteria for…

  12. What Is the Evidence for Harm of Neuromuscular Blockade and Corticosteroid Use in the Intensive Care Unit?

    PubMed

    Annane, Djillali

    2016-02-01

    Neuromuscular blocking agents and corticosteroids are widely used in medicine and in particular in the intensive care unit (ICU). Neuromuscular blockade is commonly used to ease tracheal intubation, to optimize mechanical ventilation and oxygenation in acute respiratory disorders such as status asthmaticus and acute respiratory distress syndrome (ARDS), to prevent shivering during therapeutic hypothermia, and also in patients with elevated intracranial pressure. In the ICU, patients with sepsis, ARDS, community-acquired pneumonia, exacerbation of chronic obstructive pulmonary disease, severe asthma, or trauma may receive corticosteroids. It is not rare that ICU patients receive concomitantly neuromuscular blocking drugs and corticosteroids. Among the various serious adverse reactions to these drugs, secondary infection and ICU-acquired weakness may place a burden to the health-care system by resulting in substantial cost and long-term morbidity. Both superinfections and ICU-acquired paresis are more likely when high doses of fluorinated corticosteroids are combined with prolonged treatment with a long-acting non-depolarizing neuromuscular blocker. Modern ICU practices favor lower dose of corticosteroids and very short course of short-acting curare for the management of sepsis or ARDS. Recent trials provided no evidence for increased risk of secondary infections or critical illness neuromyopathy in patients with sepsis or ARDS with the use of corticosteroids or neuromuscular blockers. PMID:26820274

  13. Central enhancement of evoked electromyographic monitoring of neuromuscular function.

    PubMed

    Smith, D C

    1991-05-01

    Central neural influences on neuromuscular transmission may explain the frequent failure of evoked electromyographic (EEMG) responses to return to control values during offset of neuromuscular block. This study, performed in conscious subjects, did not demonstrate any change in EEMG response of either the first dorsal interosseous muscle during onset of ulnar nerve block or the flexor hallucis brevis during onset of subarachnoid block. It is concluded that central enhancement of EEMG response via a neural mechanism does not explain the observed failure of EEMG monitoring of neuromuscular block.

  14. Central enhancement of evoked electromyographic monitoring of neuromuscular function.

    PubMed

    Smith, D C

    1991-05-01

    Central neural influences on neuromuscular transmission may explain the frequent failure of evoked electromyographic (EEMG) responses to return to control values during offset of neuromuscular block. This study, performed in conscious subjects, did not demonstrate any change in EEMG response of either the first dorsal interosseous muscle during onset of ulnar nerve block or the flexor hallucis brevis during onset of subarachnoid block. It is concluded that central enhancement of EEMG response via a neural mechanism does not explain the observed failure of EEMG monitoring of neuromuscular block. PMID:1851627

  15. Sugammadex: A Review of Neuromuscular Blockade Reversal.

    PubMed

    Keating, Gillian M

    2016-07-01

    Sugammadex (Bridion(®)) is a modified γ-cyclodextrin that reverses the effect of the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium. Intravenous sugammadex resulted in rapid, predictable recovery from moderate and deep neuromuscular blockade in patients undergoing surgery who received rocuronium or vecuronium. Recovery from moderate neuromuscular blockade was significantly faster with sugammadex 2 mg/kg than with neostigmine, and recovery from deep neuromuscular blockade was significantly faster with sugammadex 4 mg/kg than with neostigmine or spontaneous recovery. In addition, recovery from neuromuscular blockade was significantly faster when sugammadex 16 mg/kg was administered 3 min after rocuronium than when patients spontaneously recovered from succinylcholine. Sugammadex also demonstrated efficacy in various special patient populations, including patients with pulmonary disease, cardiac disease, hepatic dysfunction or myasthenia gravis and morbidly obese patients. Intravenous sugammadex was generally well tolerated. In conclusion, sugammadex is an important option for the rapid reversal of rocuronium- or vecuronium-induced neuromuscular blockade. PMID:27324403

  16. Neuromuscular blockade in the elderly patient

    PubMed Central

    Lee, Luis A; Athanassoglou, Vassilis; Pandit, Jaideep J

    2016-01-01

    Neuromuscular blockade is a desirable or even essential component of general anesthesia for major surgical operations. As the population continues to age, and more operations are conducted in the elderly, due consideration must be given to neuromuscular blockade in these patients to avoid possible complications. This review considers the pharmacokinetics and pharmacodynamics of neuromuscular blockade that may be altered in the elderly. Compartment distribution, metabolism, and excretion of drugs may vary due to age-related changes in physiology, altering the duration of action with a need for reduced dosage (eg, aminosteroids). Other drugs (atracurium, cisatracurium) have more reliable duration of action and should perhaps be considered for use in the elderly. The range of interpatient variability that neuromuscular blocking drugs may exhibit is then considered and drugs with a narrower range, such as cisatracurium, may produce more predictable, and inherently safer, outcomes. Ultimately, appropriate neuromuscular monitoring should be used to guide the administration of muscle relaxants so that the risk of residual neuromuscular blockade postoperatively can be minimized. The reliability of various monitoring is considered. This paper concludes with a review of the various reversal agents, namely, anticholinesterase drugs and sugammadex, and the alterations in dosing of these that should be considered for the elderly patient. PMID:27382330

  17. Novel pharmacological approaches for the antagonism of neuromuscular blockade.

    PubMed

    Pic, Lisa C

    2005-02-01

    Gamma cyclodextrin and purified plasma cholinesterase are 2 novel pharmacological agents being investigated as to their suitability for antagonism of neuromuscular blockade. Both of these agents are devoid of cholinergic stimulation and the accompanying side effects because their action is independent of acetylcholinesterase inhibition. Gamma cyclodextrin antagonizes the steroidal neuromuscular blocker rocuronium via the chemical encapsulation of the molecule forming a "host-guest" complex through van der Waals and hydrophobic interactions in the plasma. Encapsulation decreases plasma drug concentrations, shifting the neuromuscular blocking drug molecules from the neuromuscular junction back to the plasma compartment resulting in a rapid recovery of the neuromuscular function. Org 25969, a modified gamma cyclodextrin, will antagonize profound neuromuscular block induced by rocuronium in approximately 2 minutes. A commercial preparation of purified human plasma cholinesterase has been shown to be effective in reversing succinylcholine or mivacurium-induced block. Administration of exogenous plasma cholinesterase also has been shown to be effective in antagonizing mivacurium-induced neuromuscular block, cocaine toxicity, and organophosphate poisoning.

  18. Neuromuscular complications in cancer.

    PubMed

    Grisold, W; Grisold, A; Löscher, W N

    2016-08-15

    Cancer is becoming a treatable and even often curable disease. The neuromuscular system can be affected by direct tumor invasion or metastasis, neuroendocrine, metabolic, dysimmune/inflammatory, infections and toxic as well as paraneoplastic conditions. Due to the nature of cancer treatment, which frequently is based on a DNA damaging mechanism, treatment related toxic side effects are frequent and the correct identification of the causative mechanism is necessary to initiate the proper treatment. The peripheral nervous system is conventionally divided into nerve roots, the proximal nerves and plexus, the peripheral nerves (mono- and polyneuropathies), the site of neuromuscular transmission and muscle. This review is based on the anatomic distribution of the peripheral nervous system, divided into cranial nerves (CN), motor neuron (MND), nerve roots, plexus, peripheral nerve, the neuromuscular junction and muscle. The various etiologies of neuromuscular complications - neoplastic, surgical and mechanic, toxic, metabolic, endocrine, and paraneoplastic/immune - are discussed separately for each part of the peripheral nervous system. PMID:27423586

  19. Effects of aminoglycoside antibiotics on the neuromuscular junction: Part I.

    PubMed

    Yamada, S; Kuno, Y; Iwanaga, H

    1986-03-01

    The effects of aminoglycoside antibiotics (AGA) including streptomycin (SM), kanamycin (KM), gentamicin (GM), dibekacin (DKB), amikacin (AMK) and sisomycin (SISO), on the neuromuscular junction were studied by in vivo and in vitro experiments. In in vitro experiments, no effect of AGA on rat phrenic nerve diaphragm preparations was observed, but the use of the antibiotics at a high concentration exerted a slight blocking effect on the neuromuscular junction. The blocking effect of SISO and DKB on the neuromuscular junction was marked. These antibiotics were definitely found to compete with eserine in terms of the blocking effect on the neuromuscular junction, but did not compete with calcium chloride. In in vitro experiments with frog sciatic nerve and musculus sartorius preparations, DKB and SISO exerted a blocking effect on the NMJ, inducing the disappearance of action potentials and the appearance of endplate potentials (EPPs). In in vitro experiments with the preparations from Rana catesbiana frogs, SM, GM, DKB and SISO exhibited an inhibiting effect on the release of acetylcholine (ACh), a chemical neurotransmitter in neuromuscular junction, resulting in a decrease in the frequency of miniature endplate potentials (mEPPS). In in vivo experiments with rabbit sciatic tibialis anterior muscle preparations, SM, GM, DKB and SISO exerted a blocking effect on the neuromuscular junction. From the facts that the effect was augmented by the use of magnesium chloride combined with these antibiotics and that the antibiotics competed with calcium chloride and potassium chloride in terms of the blocking effect on the neuromuscular junction, the effects seemed to be due to the inhibition of ACh release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3699939

  20. Neuromuscular monitoring: old issues, new controversies.

    PubMed

    Kopman, Aaron F

    2009-03-01

    "Expert" editorial opinion suggests that objective or quantitative neuromuscular monitors should be used whenever nondepolarizing blocking agents are administered. It is clear that this advice has by and large fallen on deaf ears. A sizeable number of clinicians here (North America) and abroad (Europe) fail to use even conventional peripheral nerve stimulators routinely. This chapter will explore potential reasons for and consequences of this disconnect between academia and "the real world." Along the way, we will examine such questions as how do we define and measure adequate recovery from nondepolarizing block. What are the limitations of clinical tests of recovery such as the "head-lift test?" What is the incidence of undetected postoperative residual curarization (PORC)? Does neuromuscular monitoring reduce the frequency of PORC? How will the availability of sugammadex alter the above discussion? PMID:19272534

  1. Electrodiagnosis in neuromuscular disease.

    PubMed

    Lipa, Bethany M; Han, Jay J

    2012-08-01

    Electromyography (EMG) is an important diagnostic tool for the assessment of individuals with various neuromuscular diseases. It should be an extension of a thorough history and physical examination. Some prototypical characteristics and findings of EMG and nerve conduction studies are discussed; however, a more thorough discussion can be found in the textbooks and resources sited in the article. With an increase in molecular genetic diagnostics, EMG continues to play an important role in the diagnosis and management of patients with neuromuscular diseases and also provides a cost-effective diagnostic workup before ordering a battery of costly genetic tests.

  2. Electrodiagnosis in neuromuscular disease.

    PubMed

    Lipa, Bethany M; Han, Jay J

    2012-08-01

    Electromyography (EMG) is an important diagnostic tool for the assessment of individuals with various neuromuscular diseases. It should be an extension of a thorough history and physical examination. Some prototypical characteristics and findings of EMG and nerve conduction studies are discussed; however, a more thorough discussion can be found in the textbooks and resources sited in the article. With an increase in molecular genetic diagnostics, EMG continues to play an important role in the diagnosis and management of patients with neuromuscular diseases and also provides a cost-effective diagnostic workup before ordering a battery of costly genetic tests. PMID:22938876

  3. Genetics and Neuromuscular Diseases

    MedlinePlus

    ... Neuromuscular Diseases • ©2011 MDA cell nucleus cell chromosomes DNA Genes are made of DNA, which is stored on chromo- somes in each ... particular protein. The effects of a mutation in DNA in a person depend on many fac- tors, ...

  4. Biotherapies of neuromuscular disorders.

    PubMed

    Briand, J-F; Roy, M-O; Mourlane, F; André, C; Loux, N; Rougeau, C; Toursel, T; Braun, S

    2014-12-01

    This review focuses on the most recent data on biotherapeutic approaches, using DNA, RNA, recombinant proteins, or cells as therapeutic tools or targets for the treatment of neuromuscular diseases. Many of these novel technologies have now reached the clinical stage and have or are about to move to the market. Others, like genome editing are still in an early stage but hold great promise.

  5. 48 CFR 52.250-3 - SAFETY Act Block Designation/Certification.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... pursuant to 6 U.S.C. 442(d), as further delineated in 6 CFR 25.9, that a QATT for which a SAFETY Act... determination by DHS pursuant to 6 U.S.C. 441(b) and 6 U.S.C. 443(a), as further delineated in 6 CFR 25.4, that... review are based on the factors identified in 6 CFR 25.4(b). (e) Neither SAFETY Act designation...

  6. Computational Models for Neuromuscular Function

    PubMed Central

    Valero-Cuevas, Francisco J.; Hoffmann, Heiko; Kurse, Manish U.; Kutch, Jason J.; Theodorou, Evangelos A.

    2011-01-01

    Computational models of the neuromuscular system hold the potential to allow us to reach a deeper understanding of neuromuscular function and clinical rehabilitation by complementing experimentation. By serving as a means to distill and explore specific hypotheses, computational models emerge from prior experimental data and motivate future experimental work. Here we review computational tools used to understand neuromuscular function including musculoskeletal modeling, machine learning, control theory, and statistical model analysis. We conclude that these tools, when used in combination, have the potential to further our understanding of neuromuscular function by serving as a rigorous means to test scientific hypotheses in ways that complement and leverage experimental data. PMID:21687779

  7. Estrogenic support of motoneuron dendritic growth via the neuromuscular periphery in a sexually dimorphic motor system.

    PubMed

    Nowacek, Ari S; Sengelaub, Dale R

    2006-08-01

    The lumbar spinal cord of rats contains the sexually dimorphic, steroid-sensitive spinal nucleus of the bulbocavernosus (SNB). In males, the growth of SNB dendrites is steroid-dependent: dendrites fail to grow after castration, but grow in castrates treated with androgens or estrogens. Blocking estradiol synthesis or estrogen receptors in gonadally intact males attenuates SNB dendritic growth, suggesting that estrogens are required and must be able to act at their receptors to support normal masculine dendritic growth. However, SNB motoneurons do not accumulate estrogens, suggesting that estrogens act indirectly to support SNB dendritic growth. In this experiment, we examined whether local estrogen action in the neuromuscular periphery was involved in the postnatal development of SNB motoneurons. Motoneuron morphology was assessed in gonadally intact and castrated males. Gonadally intact males were left untreated or given either blank or tamoxifen implants sutured to the target musculature, or tamoxifen interscapular implants. Castrated males were left untreated or were given estradiol by muscle or interscapular implants or systemic injection during the period of SNB dendritic growth. At postnatal day 28, when SNB dendritic length is normally maximal, SNB motoneurons were retrogradely labeled with cholera toxin-HRP and reconstructed in three dimensions. While interscapular tamoxifen implants were ineffective, blocking estrogen receptors at the target musculature resulted in attenuation of SNB dendritic growth. In contrast, while interscapular implants of estradiol were ineffective, local treatment with estradiol at the target musculature in castrated males resulted in masculinization of dendritic growth. Thus, estrogens may act by an indirect action in the neuromuscular periphery to support SNB dendritic growth.

  8. Neuromuscular complications of acromegaly.

    PubMed

    Pickett, J B; Layzer, R B; Levin, S R; Scheider, V; Campbell, M J; Sumner, A J

    1975-07-01

    Seventeen consecutive acromegalic patients were evaluated for evidence of neuromuscular dysfunction and followed for 1 year after hypophysectomy. Before treatment, four patients had both a myopathy and the carpal tunnel syndrome, five had myopathy alone, four had carpal tunnel syndrome alone, and four had neither. The myopathy was caracterized by mild, strictly promixal weakness and flabbiness of muscles; electromyography revealed typical myopathic abnormalities, but serum enzymes and muscle biopsy usually were normal. The presence of myopathy or the carpal tunnel syndrrome could not be correlated with the magnitude of growth hormone elevation or any secondary endocrine derangement, but myopathy was associated with a longer duration of acromegaly. Carpal tunnel symptoms usually improved in the first 6 weeks after hypophysectomy, while myopathy improved more slowly and sometimes was detectable 1 year later.

  9. Evidence that the SKI antiviral system of Saccharomyces cerevisiae acts by blocking expression of viral mRNA.

    PubMed Central

    Widner, W R; Wickner, R B

    1993-01-01

    The SKI2 gene is part of a host system that represses the copy number of the L-A double-stranded RNA (dsRNA) virus and its satellites M and X dsRNA, of the L-BC dsRNA virus, and of the single-stranded replicon 20S RNA. We show that SKI2 encodes a 145-kDa protein with motifs characteristic of helicases and nucleolar proteins and is essential only in cells carrying M dsRNA. Unexpectedly, Ski2p does not repress M1 dsRNA copy number when M1 is supported by aN L-A cDNA clone; nonetheless, it did lower the levels of M1 dsRNA-encoded toxin produced. Since toxin secretion from cDNA clones of M1 is unaffected by Ski2p, these data suggest that Ski2p acts by specifically blocking translation of viral mRNAs, perhaps recognizing the absence of cap or poly(A). In support of this idea, we find that Ski2p represses production of beta-galactosidase from RNA polymerase I [no cap and no poly(A)] transcripts but not from RNA polymerase II (capped) transcripts. Images PMID:8321235

  10. Neuromuscular disease classification system

    NASA Astrophysics Data System (ADS)

    Sáez, Aurora; Acha, Begoña; Montero-Sánchez, Adoración; Rivas, Eloy; Escudero, Luis M.; Serrano, Carmen

    2013-06-01

    Diagnosis of neuromuscular diseases is based on subjective visual assessment of biopsies from patients by the pathologist specialist. A system for objective analysis and classification of muscular dystrophies and neurogenic atrophies through muscle biopsy images of fluorescence microscopy is presented. The procedure starts with an accurate segmentation of the muscle fibers using mathematical morphology and a watershed transform. A feature extraction step is carried out in two parts: 24 features that pathologists take into account to diagnose the diseases and 58 structural features that the human eye cannot see, based on the assumption that the biopsy is considered as a graph, where the nodes are represented by each fiber, and two nodes are connected if two fibers are adjacent. A feature selection using sequential forward selection and sequential backward selection methods, a classification using a Fuzzy ARTMAP neural network, and a study of grading the severity are performed on these two sets of features. A database consisting of 91 images was used: 71 images for the training step and 20 as the test. A classification error of 0% was obtained. It is concluded that the addition of features undetectable by the human visual inspection improves the categorization of atrophic patterns.

  11. Neuromuscular disease classification system.

    PubMed

    Sáez, Aurora; Acha, Begoña; Montero-Sánchez, Adoración; Rivas, Eloy; Escudero, Luis M; Serrano, Carmen

    2013-06-01

    Diagnosis of neuromuscular diseases is based on subjective visual assessment of biopsies from patients by the pathologist specialist. A system for objective analysis and classification of muscular dystrophies and neurogenic atrophies through muscle biopsy images of fluorescence microscopy is presented. The procedure starts with an accurate segmentation of the muscle fibers using mathematical morphology and a watershed transform. A feature extraction step is carried out in two parts: 24 features that pathologists take into account to diagnose the diseases and 58 structural features that the human eye cannot see, based on the assumption that the biopsy is considered as a graph, where the nodes are represented by each fiber, and two nodes are connected if two fibers are adjacent. A feature selection using sequential forward selection and sequential backward selection methods, a classification using a Fuzzy ARTMAP neural network, and a study of grading the severity are performed on these two sets of features. A database consisting of 91 images was used: 71 images for the training step and 20 as the test. A classification error of 0% was obtained. It is concluded that the addition of features undetectable by the human visual inspection improves the categorization of atrophic patterns. PMID:23804164

  12. Maintaining Optimal Surgical Conditions With Low Insufflation Pressures is Possible With Deep Neuromuscular Blockade During Laparoscopic Colorectal Surgery

    PubMed Central

    Kim, Myoung Hwa; Lee, Ki Young; Lee, Kang-Young; Min, Byung-Soh; Yoo, Young Chul

    2016-01-01

    Abstract Carbon dioxide (CO2) absorption and increased intra-abdominal pressure can adversely affect perioperative physiology and postoperative recovery. Deep muscle relaxation is known to improve the surgical conditions during laparoscopic surgery. We aimed to compare the effects of deep and moderate neuromuscular block in laparoscopic colorectal surgery, including intra-abdominal pressure. In this prospective, double-blind, parallel-group trial, 72 adult patients undergoing laparoscopic colorectal surgery were randomized using an online randomization generator to achieve either moderate (1–2 train-of-four response, n = 36) or deep (1–2 post-tetanic count, n = 36) neuromuscular block by receiving a continuous infusion of rocuronium. Adjusted intra-abdominal pressure, which was titrated by a surgeon with maintaining the operative field during pneumoperitoneum, was recorded at 5-minute intervals. Perioperative hemodynamic parameters and postoperative outcomes were assessed. Six patients from the deep and 5 from the moderate neuromuscular block group were excluded, leaving 61 for analysis. The average adjusted IAP was lower in the deep compared to the moderate neuromuscular block group (9.3 vs 12 mm Hg, P < 0.001). The postoperative pain scores (P < 0.001) and incidence of postoperative shoulder tip pain were lower, whereas gas passing time (P = 0.002) and sips of water time (P = 0.005) were shorter in the deep neuromuscular block than in the moderate neuromuscular block group. Deep neuromuscular blocking showed several benefits compared to conventional moderate neuromuscular block, including a greater intra-abdominal pressure lowering effect, whereas surgical conditions are maintained, less severe postoperative pain and faster bowel function recovery. PMID:26945393

  13. Sevoflurane enhances neuromuscular blockade by increasing the sensitivity of skeletal muscle to neuromuscular blockers

    PubMed Central

    Ye, Ling; Zuo, Yunxia; Zhang, Peng; Yang, Pingliang

    2015-01-01

    The aim of this study was to investigate the effects of sevoflurane on skeletal muscle contractility. In the first part, twenty-two American Society of Anesthesiology (ASA I-II) female adult patients undergoing elective hysterectomy surgery inhaled sevoflurane 1.0, 1.5 and 2.0 minimum alveolar concentrations (MAC) in succession. Neuromuscular function was assessed at each dose. In the second part, forty-four ASA I-II female adult patients were randomized into four groups: group 1 (propofol + atracurium, sevoflurane 0 MAC), and groups 2 to 4 (atracurium + sevoflurane 1.0, 1.5 and 2.0 MAC, respectively). In group 1, patients were anesthetized by propofol. Then 0.01 mg/kg atracurium was injected into the tested arm intravenously after the arterial blood flow was blocked using a tourniquet. For the other 3 groups, patients inhaled 1.0 MAC, 1.5 MAC, or 2.0 MAC of sevoflurane. Then 0.01 mg/kg atracurium was injected. Neuromuscular function was recorded for the 4 groups. Neuromuscular function was assessed by acceleromyography measurement of evoked responses to train-of four (TOF) stimuli (2 Hz for 2 s applied every 12 s) at the adductor pollicis using a TOF-GuardTM neuromuscular transmission monitor. Amplitudes of first response (T1) in each TOF sequence and the ratios of fourth TOF response (T4) to the first were similar at 1.0 MAC, 1.5 MAC, and 2.0 MAC sevoflurane. Compared to baseline, there was no significant change in the TOF value after inhaling 1.0 MAC, 1.5 MAC, or 2.0 MAC sevoflurane. Compared to group 1, there was no significant difference in atracurium onset time (time to reach TOF ratio = 0.25) in group 2 ( 5.6 ± 1.8 min vs. 6.5 ± 1.7 min, P>0.05), or degree of adductor pollicis block (subject number with TOF ratio = 0, 5 vs. 2 subjects, p = 0.3). However, inhaling 1.5 or 2.0 MAC sevoflurane decreased atracurium onset time (4.6 ± 1.5 min and 4.0 ± 1.3 min vs. 6.5 ± 1.7 min, P<0.01 and P<0.001, respectively), and enhanced the block degree (9 and 10 vs. 2

  14. Neuromuscular ultrasound of cranial nerves.

    PubMed

    Tawfik, Eman A; Walker, Francis O; Cartwright, Michael S

    2015-04-01

    Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.

  15. Activation of Matrix Metalloproteinase-3 is altered at the frog neuromuscular junction following changes in synaptic activity.

    PubMed

    VanSaun, M; Humburg, B C; Arnett, M G; Pence, M; Werle, M J

    2007-09-15

    The extracellular matrix surrounding the neuromuscular junction is a highly specialized and dynamic structure. Matrix Metalloproteinases are enzymes that sculpt the extracellular matrix. Since synaptic activity is critical to the structure and function of this synapse, we investigated whether changes in synaptic activity levels could alter the activity of Matrix Metalloproteinases at the neuromuscular junction. In particular, we focused on Matrix Metalloproteinase 3 (MMP3), since antibodies to MMP3 recognize molecules at the frog neuromuscular junction, and MMP3 cleaves a number of synaptic basal lamina molecules, including agrin. Here we show that the fluorogenic compound (M2300) can be used to perform in vivo proteolytic imaging of the frog neuromuscular junction to directly measure the activity state of MMP3. Application of this compound reveals that active MMP3 is concentrated at the normal frog neuromuscular junction, and is tightly associated with the terminal Schwann cell. Blocking presynaptic activity via denervation, or TTX nerve blockade, results in a decreased level of active MMP3 at the neuromuscular junction. The loss of active MMP3 at the neuromuscular junction in denervated muscles can result from decreased activation of pro-MMP3, or it could result from increased inhibition of MMP3. These results support the hypothesis that changes in synaptic activity can alter the level of active MMP3 at the neuromuscular junction. PMID:17525979

  16. Effect of 50% enantiomeric excess bupivacaine mixture combined with pancuronium on neuromuscular transmission in rat phrenic nerve-diaphragm preparation; a pilot study

    PubMed Central

    de Assunção Braga, Angelica de Fátima; Carvalho, Vanessa Henriques; da Silva Braga, Franklin Sarmento; Potério, Gloria Maria Braga; Santos, Filipe Nadir Caparica; Junqueira, Fernando Eduardo Féres

    2015-01-01

    Background and Aims: Local anaesthetics are drugs that are widely used in clinical practice. However, the effects of these drugs on the neuromuscular junction and their influence on the blockade produced by non-depolarising neuromuscular blocking drugs are still under investigation. The aim of this study was to evaluate, in vitro, the influence of a 50% enantiomeric excess bupivacaine mixture on neuromuscular transmission and neuromuscular block produced by pancuronium. Methods: Rats were distributed into three groups (n = 5) according to the drug studied namely, 50% enantiomeric excess bupivacaine mixture (5 μg/mL); pancuronium (2 μg/mL); 50% enantiomeric excess bupivacaine mixture + pancuronium. The following parameters were evaluated: (1) Effects of a 50% enantiomeric excess bupivacaine mixture on membrane potential (MP) and miniature endplate potentials (MEPPs); (2) amplitude of diaphragmatic response before and 60 min after the addition of a 50% enantiomeric excess bupivacaine mixture; the degree of neuromuscular block with pancuronium and pancuronium combined with a 50% enantiomeric excess bupivacaine mixture. Results: A 50% enantiomeric excess bupivacaine mixture did not alter the amplitude of muscle response (MP) but decreased the frequency and amplitude of MEPP. The block produced by pancuronium was potentiated by a 50% enantiomeric excess bupivacaine mixture. Conclusion: A 50% enantiomeric excess bupivacaine mixture used alone did not affect neuromuscular transmission, but potentiated the neuromuscular block produced by pancuronium. No action was shown on the muscle fibre, and alterations on MEPPs demonstrated a presynaptic action. PMID:26755834

  17. DYNAMIC NEUROMUSCULAR STABILIZATION & SPORTS REHABILITATION

    PubMed Central

    Kobesova, Alena; Kolar, Pavel

    2013-01-01

    Dynamic neuromuscular (core) stability is necessary for optimal athletic performance and is not achieved purely by adequate strength of abdominals, spinal extensors, gluteals or any other musculature; rather, core stabilization is accomplished through precise coordination of these muscles and intra‐abdominal pressure regulation by the central nervous system. Understanding developmental kinesiology provides a framework to appreciate the regional interdependence and the inter‐linking of the skeleton, joints, musculature during movement and the importance of training both the dynamic and stabilizing function of muscles in the kinetic chain. The Dynamic Neuromuscular Stabilization (DNS) approach provides functional tools to assess and activate the intrinsic spinal stabilizers in order to optimize the movement system for both pre‐habilitation and rehabilitation of athletic injuries and performance. Level of Evidence: 5 PMID:23439921

  18. Neuromuscular fatigue in racquet sports.

    PubMed

    Girard, Olivier; Millet, Grégoire P

    2008-02-01

    This article describes the physiologic and neural mechanisms that cause neuromuscular fatigue in racquet sports: table tennis, tennis, squash, and badminton. In these intermittent and dual activities, performance may be limited as a match progresses because of a reduced central activation, linked to changes in neurotransmitter concentration or in response to afferent sensory feedback. Alternatively, modulation of spinal loop properties may occur because of changes in metabolic or mechanical properties within the muscle. Finally, increased fatigue manifested by mistimed strokes, lower speed, and altered on-court movements may be caused by ionic disturbances and impairments in excitation-contraction coupling properties. These alterations in neuromuscular function contribute to decrease in racquet sports performance observed under fatigue.

  19. [Respiratory treatments in neuromuscular disease].

    PubMed

    Martínez Carrasco, C; Cols Roig, M; Salcedo Posadas, A; Sardon Prado, O; Asensio de la Cruz, O; Torrent Vernetta, A

    2014-10-01

    In a previous article, a review was presented of the respiratory pathophysiology of the patient with neuromuscular disease, as well as their clinical evaluation and the major complications causing pulmonary deterioration. This article presents the respiratory treatments required to preserve lung function in neuromuscular disease as long as possible, as well as in special situations (respiratory infections, spinal curvature surgery, etc.). Special emphasis is made on the use of non-invasive ventilation, which is changing the natural history of many of these diseases. The increase in survival and life expectancy of these children means that they can continue their clinical care in adult units. The transition from pediatric care must be an active, timely and progressive process. It may be slightly stressful for the patient before the adaptation to this new environment, with multidisciplinary care always being maintained.

  20. Neuromuscular fatigue in racquet sports.

    PubMed

    Girard, Olivier; Millet, Grégoire P

    2009-02-01

    This article describes the physiologic and neural mechanisms that cause neuromuscular fatigue in racquet sports: table tennis, tennis, squash, and badminton. In these intermittent and dual activities, performance may be limited as a match progresses because of a reduced central activation, linked to changes in neurotransmitter concentration or in response to afferent sensory feedback. Alternatively, modulation of spinal loop properties may occur because of changes in metabolic or mechanical properties within the muscle. Finally, increased fatigue manifested by mistimed strokes, lower speed, and altered on-court movements may be caused by ionic disturbances and impairments in excitation-contraction coupling properties. These alterations in neuromuscular function contribute to decrease in racquet sports performance observed under fatigue.

  1. Neuromuscular Disease Models and Analysis.

    PubMed

    Burgess, Robert W; Cox, Gregory A; Seburn, Kevin L

    2016-01-01

    Neuromuscular diseases can affect the survival of peripheral neurons, their axons extending to peripheral targets, their synaptic connections onto those targets, or the targets themselves. Examples include motor neuron diseases such as Amyotrophic Lateral Sclerosis, peripheral neuropathies such as Charcot-Marie-Tooth diseases, myasthenias, and muscular dystrophies. Characterizing these phenotypes in mouse models requires an integrated approach, examining both the nerve and muscle histologically, anatomically, and functionally by electrophysiology. Defects observed at these levels can be related back to onset, severity, and progression, as assessed by "Quality of life measures" including tests of gross motor performance such as gait or grip strength. This chapter describes methods for assessing neuromuscular disease models in mice, and how interpretation of these tests can be complicated by the inter-relatedness of the phenotypes. PMID:27150099

  2. [Respiratory treatments in neuromuscular disease].

    PubMed

    Martínez Carrasco, C; Cols Roig, M; Salcedo Posadas, A; Sardon Prado, O; Asensio de la Cruz, O; Torrent Vernetta, A

    2014-10-01

    In a previous article, a review was presented of the respiratory pathophysiology of the patient with neuromuscular disease, as well as their clinical evaluation and the major complications causing pulmonary deterioration. This article presents the respiratory treatments required to preserve lung function in neuromuscular disease as long as possible, as well as in special situations (respiratory infections, spinal curvature surgery, etc.). Special emphasis is made on the use of non-invasive ventilation, which is changing the natural history of many of these diseases. The increase in survival and life expectancy of these children means that they can continue their clinical care in adult units. The transition from pediatric care must be an active, timely and progressive process. It may be slightly stressful for the patient before the adaptation to this new environment, with multidisciplinary care always being maintained. PMID:24890888

  3. Tests of gastric neuromuscular function.

    PubMed

    Parkman, Henry P; Jones, Michael P

    2009-05-01

    Tests of gastric neuromuscular function are used to evaluate patients with symptoms referable to the upper digestive tract. These symptoms can be associated with alterations in the rates of gastric emptying, impaired accommodation, heightened gastric sensation, or alterations in gastric myoelectrical function and contractility. Management of gastric neuromuscular disorders requires an understanding of pathophysiology and treatment options as well as the appropriate use and interpretation of diagnostic tests. These tests include measures of gastric emptying; contractility; electrical activity; regional gastric motility of the fundus, antrum, and pylorus; and tests of sensation and compliance. Tests are also being developed to improve our understanding of the afferent sensory pathways from the stomach to the central nervous system that mediate gastric sensation in health and gastric disorders. This article reviews tests of gastric function and provides a basic description of the tests, the methodologies behind them, descriptions of the physiology that they assess, and their clinical utility. PMID:19293005

  4. Neuromuscular ultrasound in common entrapment neuropathies.

    PubMed

    Cartwright, Michael S; Walker, Francis O

    2013-11-01

    Neuromuscular ultrasound involves the use of high-resolution ultrasound to image the peripheral nervous system of patients with suspected neuromuscular diseases. It complements electrodiagnostic studies well by providing anatomic information regarding nerves, muscles, vessels, tendons, ligaments, bones, and other structures that cannot be obtained with nerve conduction studies and electromyography. Neuromuscular ultrasound has been studied extensively over the past 10 years and has been used most often in the assessment of entrapment neuropathies. This review focuses on the use of neuromuscular ultrasound in 4 of the most common entrapment neuropathies: carpal tunnel syndrome, ulnar neuropathy at the elbow and wrist, and fibular neuropathy at the knee.

  5. Rocuronium and sugammadex in a 3 days old neonate for draining an ovarian cyst. Neuromuscular management and review of the literature.

    PubMed

    Carlos, Ricardo Vieira; Torres, Marcelo Luis Abramides; de Boer, Hans D

    2016-01-01

    A case is reported in which a 3-days old neonate with a giant ovarian cyst was scheduled for surgery. The patient received a dose of sugammadex to reverse a rocuronium-induced neuromuscular block. A fast and efficient recovery from neuromuscular block was achieved within 90s. No adverse events or other safety concerns were observed. Furthermore, a review of the literature on the use of sugammadex in neonates was performed.

  6. [Rocuronium and sugammadex in a 3 days old neonate for draining an ovarian cyst. Neuromuscular management and review of the literature].

    PubMed

    Carlos, Ricardo Vieira; Torres, Marcelo Luis Abramides; de Boer, Hans D

    2016-01-01

    A case is reported in which a 3-days old neonate with a giant ovarian cyst was scheduled for surgery. The patient received a dose of sugammadex to reverse a rocuronium-induced neuromuscular block. A fast and efficient recovery from neuromuscular block was achieved within 90s. No adverse events or other safety concerns were observed. Furthermore, a review of the literature on the use of sugammadex in neonates was performed.

  7. Triethylcholine compared with other substances affecting neuromuscular transmission

    PubMed Central

    Bowman, W. C.; Hemsworth, B. A.; Rand, M. J.

    1962-01-01

    Triethylcholine (triethyl-2-hydroxyethyl ammonium) has been compared, in its actions on neuromuscular transmission, with the motor end-plate blocking drugs tubocurarine and decamethonium, with the anticholinesterase neostigmine, and with the closely related drug tetraethylammonium. The experiments were carried out on conscious rabbits and mice, on the tibialis anterior muscle of cats under chloralose anaesthesia and on the isolated phrenic nerve-diaphragm preparation of the rat. Anticholinesterase activity was determined manometrically using the Warburg apparatus. Triethylcholine possessed a slight curare-like action, but this effect was shown to be too weak and transient to contribute to the slowly developing and long-lasting transmission failure which occurs selectively in frequently excited nervemuscle preparations and in exercised conscious animals. It was confirmed that the site of the blocking action of triethylcholine was pre-junctional. Triethylcholine often produced a slight potentiation of the contractions before blocking them. This effect was not due to a depolarizing or an anticholinesterase action, and it was concluded that the slight initial facilitating action of triethylcholine on neuromuscular transmission was due to an increase in the quantity of acetylcholine released by the nerve impulse. Tetraethylammonium was much more powerful than triethylcholine in this respect. The pre-junctional transmission failure produced by triethylcholine could not be explained simply on the basis that an initial excessive release led to exhaustion of transmitter. ImagesFig. 7 PMID:13872106

  8. Inhibitory responses in Aplysia pleural sensory neurons act to block excitability, transmitter release, and PKC Apl II activation.

    PubMed

    Dunn, Tyler W; Farah, Carole A; Sossin, Wayne S

    2012-01-01

    Expression of the 5-HT(1Apl(a)) receptor in Aplysia pleural sensory neurons inhibited 5-HT-mediated translocation of the novel PKC Apl II in sensory neurons and prevented PKC-dependent synaptic facilitation at sensory to motoneuron synapses (Nagakura et al. 2010). We now demonstrate that the ability of inhibitory receptors to block PKC activation is a general feature of inhibitory receptors and is found after expression of the 5-HT(1Apl(b)) receptor and with activation of endogenous dopamine and FMRFamide receptors in sensory neurons. Pleural sensory neurons are heterogeneous for their inhibitory response to endogenous transmitters, with dopamine being the most prevalent, followed by FMRFamide, and only a small number of neurons with inhibitory responses to 5-HT. The inhibitory response is dominant, reduces membrane excitability and synaptic efficacy, and can reverse 5-HT facilitation at both naive and depressed synapses. Indeed, dopamine can reverse PKC translocation during the continued application of 5-HT. Reversal of translocation can also be seen after translocation mediated by an analog of diacylglycerol, suggesting inhibition is not through blockade of diacylglycerol production. The effects of inhibition on PKC translocation can be rescued by phosphatidic acid, consistent with the inhibitory response involving a reduction or block of production of this lipid. However, phosphatidic acid could not recover PKC-dependent synaptic facilitation due to an additional inhibitory effect on the non-L-type calcium flux linked to synaptic transmission. In summary, we find a novel mechanism downstream of inhibitory receptors linked to inhibition of PKC activation in Aplysia sensory neurons. PMID:21994260

  9. Common complications of pediatric neuromuscular disorders.

    PubMed

    Skalsky, Andrew J; Dalal, Pritha B

    2015-02-01

    Children with pediatric neuromuscular disorders experience common complications, primarily due to immobility and weakness. Musculoskeletal complications include hip dysplasia with associated hip subluxation or dislocation, neuromuscular scoliosis, and osteoporosis and resulting fractures. Constipation, gastroesophageal reflux, and obesity and malnutrition are commonly experienced gastrointestinal complications. Disordered sleep also is frequently observed, which affects both patients and caregivers. PMID:25479776

  10. Neuromuscular Control and Coordination during Cycling

    ERIC Educational Resources Information Center

    Li, Li

    2004-01-01

    The neuromuscular control aspect of cycling has been investigated through the effects of modifying posture and cadence. These studies show that changing posture has a more profound influence on neuromuscular coordination than does changing slope. Most of the changes with standing posture occur late in the downstroke: increased ankle and knee joint…

  11. Length heterogeneity at conserved sequence block 2 in human mitochondrial DNA acts as a rheostat for RNA polymerase POLRMT activity

    PubMed Central

    Tan, Benedict G.; Wellesley, Frederick C.; Savery, Nigel J.; Szczelkun, Mark D.

    2016-01-01

    The guanine (G)-tract of conserved sequence block 2 (CSB 2) in human mitochondrial DNA can result in transcription termination due to formation of a hybrid G-quadruplex between the nascent RNA and the nontemplate DNA strand. This structure can then influence genome replication, stability and localization. Here we surveyed the frequency of variation in sequence identity and length at CSB 2 amongst human mitochondrial genomes and used in vitro transcription to assess the effects of this length heterogeneity on the activity of the mitochondrial RNA polymerase, POLRMT. In general, increased G-tract length correlated with increased termination levels. However, variation in the population favoured CSB 2 sequences which produced efficient termination while particularly weak or strong signals were avoided. For all variants examined, the 3′ end of the transcripts mapped to the same downstream sequences and were prevented from terminating by addition of the transcription factor TEFM. We propose that CSB 2 length heterogeneity allows variation in the efficiency of transcription termination without affecting the position of the products or the capacity for regulation by TEFM. PMID:27436287

  12. DNA repair after ultraviolet irradiation of ICR 2A frog cells: pyrimidine dimers are long acting blocks to nascent DNA synthesis

    SciTech Connect

    Rosenstein, B.S.; Setlow, R.B.

    1980-08-01

    The ability of ICR 2A frog cells to repair DNA damage induced by ultraviolet irradiation was examined. These cells are capable of photoreactivation but are nearly totally deficient in excision repair. They have the ability to convert the small molecular weight DNA made after irradiation into large molecules but do not show an enhancement in this process when the UV dose is delivered in two separate exposures separated by a 3- or 24-h incubation. Total DNA synthesis is depressed and low molecular weight DNA continues to be synthesized during pulse-labeling as long as 48 h after irradiation. The effects of pyrimidine dimer removal through exposure of UV irradiated cells to photoreactivating light indicate that dimers act as the critical lesions blocking DNA synthesis.

  13. Effects of mescaline and some of its analogs on cholinergic neuromuscular transmission.

    PubMed

    Ghansah, E; Kopsombut, P; Malleque, M A; Brossi, A

    1993-02-01

    Mescaline (3,4,5-trimethoxyphenylethylamine; MES) and its analogs, anhalinine (ANH) and methylenemescaline trimer (MMT) were investigated, using sciatic-sartorius preparations of the frog and cortical tissue from the rat. The effects of MES and its analogs were examined with respect to muscle twitch, resting membrane potential and nicotinic receptor binding. Mescaline and its analogs (10-100 microM) blocked both directly and neurally evoked twitches but their effects on neurally evoked twitches were greater than those on directly evoked twitches. Mescaline, ANH and MMT decreased amplitude of the miniature endplate and endplate potentials, decreased acetylcholine (ACh) quantal content, hyperpolarized the resting membrane potential and prolonged duration of the action potential. They did not significantly displace the binding of [125I]-alpha-bungarotoxin (alpha-BTX) to nicotinic receptors, at concentrations which blocked neuromuscular transmission. These results suggest that MES and its analogs inhibit cholinergic neuromuscular transmission by blocking release of ACh; they also affect K+ conductance.

  14. Neuromuscular Highlights-AAN 2005.

    PubMed

    Cheema, Zahid; Saperstein, David; Jackson, Carolyn; Newman, Daniel

    2006-06-01

    Summary of Neuromuscular Presentations at the 57 Annual AAN 2005 meeting in Miami Florida on topics of Facioscapulohumeral muscular dystrophy (FSHD), Duchenne muscular dystrophy (DMD), Diabetic Neuropathy, Charco Marie Tooth disease (CMT), Comparison of injected steroids versus Surgery for carpal tunnel syndrome, Rituximab in Anti-MAG associated polyneuropathy, Cannabis based medicine (CBM) in the treatment of neuropathic pain, utility of skin biopsy with intraepidermal nerve fiber density (IENFD) in sensory complaints, comparing sympathetic skin responses (SSRs) and skin biopsy in diagnosing small fiber sensory neuropathy, Chronic inflammatory demyelinating polyneuropathy (CIDP) clinical and electrophysiologic predictors, affect of limb warming in mild ulnar nerve conduction study (NCS) abnormalities, Tamoxifen affect in ALS, open label study of 3,4 DAP, Pyridostigmine and Ephedrine in fast channel syndrome, Mexilitine as an antimyotonia treatment in myotonic dystrophy (DM1), frontal lobe impairment evaluation in DM1 and DM2 patients and phenotype-genotype correlation in patients with dysferlinopathy. PMID:19078809

  15. Measurement of acceleration: a new method of monitoring neuromuscular function.

    PubMed

    Viby-Mogensen, J; Jensen, E; Werner, M; Nielsen, H K

    1988-01-01

    A new method for monitoring neuromuscular function based on measurement of acceleration is presented. The rationale behind the method is Newton's second law, stating that the acceleration is directly proportional to the force. For measurement of acceleration, a piezo-electric ceramic wafer was used. When this piezo electrode was fixed to the thumb, an electrical signal proportional to the acceleration was produced whenever the thumb moved in response to nerve stimulation. The electrical signal was registered and analysed in a Myograph 2000 neuromuscular transmission monitor. In 35 patients anaesthetized with halothane, train-of-four ratios measured with the accelerometer (ACT-TOF) were compared with simultaneous mechanical train-of-four ratios (FDT-TOF). Control ACT-TOF ratios were significantly higher than control FDT-TOF ratios: 116 +/- 12 and 98 +/- 4 (mean +/- s.d.), respectively. In five patients not given any relaxant during the anaesthetic procedure (20-60 min), both responses were remarkably constant. In 30 patients given vecuronium, a close linear relationship was found during recovery between ACT-TOF and FDT-TOF ratios. It is concluded that the method fulfils the basic requirements for a simple and reliable clinical monitoring tool.

  16. Novel drug development for neuromuscular blockade

    PubMed Central

    Prabhakar, Amit; Kaye, Alan D; Wyche, Melville Q; Salinas, Orlando J; Mancuso, Kenneth; Urman, Richard D

    2016-01-01

    Pharmacological advances in anesthesia in recent decades have resulted in safer practice and better outcomes. These advances include improvement in anesthesia drugs with regard to efficacy and safety profiles. Although neuromuscular blockers were first introduced over a half century ago, few new neuromuscular blockers and reversal agents have come to market and even fewer have remained as common clinically employed medications. In recent years, newer agents have been studied and are presented in this review. With regard to nondepolarizer neuromuscular blocker agents, the enantiomers Gantacurium and CW002, which are olefinic isoquinolinium diester fumarates, have shown potential for clinical application. Advantages include ultra rapid reversal of neuromuscular blockade via cysteine adduction and minimal systemic hemodynamic effects with administration. PMID:27625489

  17. School Intervention for the Neuromuscularly Handicapped Child.

    ERIC Educational Resources Information Center

    Hall, Colin D.; Porter, Patricia

    1983-01-01

    Difficulties encountered in school by 35 neuromuscularly handicapped children, (5 to 18 years old) were assessed, and methods of alleviating problems were developed. (SEW) Journal Availability: The C. V. Mosby Company, 11830 Westline Industrial Drive, St. Louis, MO 63141.

  18. Novel drug development for neuromuscular blockade

    PubMed Central

    Prabhakar, Amit; Kaye, Alan D; Wyche, Melville Q; Salinas, Orlando J; Mancuso, Kenneth; Urman, Richard D

    2016-01-01

    Pharmacological advances in anesthesia in recent decades have resulted in safer practice and better outcomes. These advances include improvement in anesthesia drugs with regard to efficacy and safety profiles. Although neuromuscular blockers were first introduced over a half century ago, few new neuromuscular blockers and reversal agents have come to market and even fewer have remained as common clinically employed medications. In recent years, newer agents have been studied and are presented in this review. With regard to nondepolarizer neuromuscular blocker agents, the enantiomers Gantacurium and CW002, which are olefinic isoquinolinium diester fumarates, have shown potential for clinical application. Advantages include ultra rapid reversal of neuromuscular blockade via cysteine adduction and minimal systemic hemodynamic effects with administration.

  19. Novel drug development for neuromuscular blockade.

    PubMed

    Prabhakar, Amit; Kaye, Alan D; Wyche, Melville Q; Salinas, Orlando J; Mancuso, Kenneth; Urman, Richard D

    2016-01-01

    Pharmacological advances in anesthesia in recent decades have resulted in safer practice and better outcomes. These advances include improvement in anesthesia drugs with regard to efficacy and safety profiles. Although neuromuscular blockers were first introduced over a half century ago, few new neuromuscular blockers and reversal agents have come to market and even fewer have remained as common clinically employed medications. In recent years, newer agents have been studied and are presented in this review. With regard to nondepolarizer neuromuscular blocker agents, the enantiomers Gantacurium and CW002, which are olefinic isoquinolinium diester fumarates, have shown potential for clinical application. Advantages include ultra rapid reversal of neuromuscular blockade via cysteine adduction and minimal systemic hemodynamic effects with administration. PMID:27625489

  20. Drosophila S6 Kinase Like Inhibits Neuromuscular Junction Growth by Downregulating the BMP Receptor Thickveins

    PubMed Central

    Zhao, Guoli; Wu, Yingga; Du, Li; Li, Wenhua; Xiong, Ying; Yao, Aiyu; Wang, Qifu; Zhang, Yong Q.

    2015-01-01

    Synaptic connections must be precisely controlled to ensure proper neural circuit formation. In Drosophila melanogaster, bone morphogenetic protein (BMP) promotes growth of the neuromuscular junction (NMJ) by binding and activating the BMP ligand receptors wishful thinking (Wit) and thickveins (Tkv) expressed in motor neurons. We report here that an evolutionally conserved, previously uncharacterized member of the S6 kinase (S6K) family S6K like (S6KL) acts as a negative regulator of BMP signaling. S6KL null mutants were viable and fertile but exhibited more satellite boutons, fewer and larger synaptic vesicles, larger spontaneous miniature excitatory junctional potential (mEJP) amplitudes, and reduced synaptic endocytosis at the NMJ terminals. Reducing the gene dose by half of tkv in S6KL mutant background reversed the NMJ overgrowth phenotype. The NMJ phenotypes of S6KL mutants were accompanied by an elevated level of Tkv protein and phosphorylated Mad, an effector of the BMP signaling pathway, in the nervous system. In addition, Tkv physically interacted with S6KL in cultured S2 cells. Furthermore, knockdown of S6KL enhanced Tkv expression, while S6KL overexpression downregulated Tkv in cultured S2 cells. This latter effect was blocked by the proteasome inhibitor MG132. Our results together demonstrate for the first time that S6KL regulates synaptic development and function by facilitating proteasomal degradation of the BMP receptor Tkv. PMID:25748449

  1. Molecular mechanisms of treadmill therapy on neuromuscular atrophy induced via botulinum toxin A.

    PubMed

    Tsai, Sen-Wei; Chen, Hsiao-Ling; Chang, Yi-Chun; Chen, Chuan-Mu

    2013-01-01

    Botulinum toxin A (BoNT-A) is a bacterial zinc-dependent endopeptidase that acts specifically on neuromuscular junctions. BoNT-A blocks the release of acetylcholine, thereby decreasing the ability of a spastic muscle to generate forceful contraction, which results in a temporal local weakness and the atrophy of targeted muscles. BoNT-A-induced temporal muscle weakness has been used to manage skeletal muscle spasticity, such as poststroke spasticity, cerebral palsy, and cervical dystonia. However, the combined effect of treadmill exercise and BoNT-A treatment is not well understood. We previously demonstrated that for rats, following BoNT-A injection in the gastrocnemius muscle, treadmill running improved the recovery of the sciatic functional index (SFI), muscle contraction strength, and compound muscle action potential (CMAP) amplitude and area. Treadmill training had no influence on gastrocnemius mass that received BoNT-A injection, but it improved the maximal contraction force of the gastrocnemius, and upregulation of GAP-43, IGF-1, Myo-D, Myf-5, myogenin, and acetylcholine receptor (AChR) subunits α and β was found following treadmill training. Taken together, these results suggest that the upregulation of genes associated with neurite and AChR regeneration following treadmill training may contribute to enhanced gastrocnemius strength recovery following BoNT-A injection.

  2. Laparoscopic surgery and muscle relaxants: is deep block helpful?

    PubMed

    Kopman, Aaron F; Naguib, Mohamed

    2015-01-01

    It has been hypothesized that providing deep neuromuscular block (a posttetanic count of 1 or more, but a train-of-four [TOF] count of zero) when compared with moderate block (TOF counts of 1-3) for laparoscopic surgery would allow for the use of lower inflation pressures while optimizing surgical space and enhancing patient safety. We conducted a literature search on 6 different medical databases using 3 search strategies in each database in an attempt to find data substantiating this proposition. In addition, we studied the reference lists of the articles retrieved in the search and of other relevant articles known to the authors. There is some evidence that maintaining low inflation pressures during intra-abdominal laparoscopic surgery may reduce postoperative pain. Unfortunately most of the studies that come to these conclusions give few if any details as to the anesthetic protocol or the management of neuromuscular block. Performing laparoscopic surgery under low versus standard pressure pneumoperitoneum is associated with no difference in outcome with respect to surgical morbidity, conversion to open cholecystectomy, hemodynamic effects, length of hospital stay, or patient satisfaction. There is a limit to what deep neuromuscular block can achieve. Attempts to perform laparoscopic cholecystectomy at an inflation pressure of 8 mm Hg are associated with a 40% failure rate even at posttetanic counts of 1 or less. Well-designed studies that ask the question "is deep block superior to moderate block vis-à-vis surgical operating conditions" are essentially nonexistent. Without exception, all the peer-reviewed studies we uncovered which state that they investigated this issue have such serious flaws in their protocols that the authors' conclusions are suspect. However, there is evidence that abdominal compliance was not increased by a significant amount when deep block was established when compared with moderate neuromuscular block. Maintenance of deep block for

  3. Rapid synthesis of acetylcholine receptors at neuromuscular junctions.

    PubMed

    Ramsay, D A; Drachman, D B; Pestronk, A

    1988-10-11

    The rate of acetylcholine receptor (AChR) degradation in mature, innervated mammalian neuromuscular junctions has recently been shown to be biphasic; up to 20% are rapidly turned over (RTOs; half life less than 1 day) whereas the remainder are lost more slowly ('stable' AChRs; half life 10-12 days). In order to maintain normal junctional receptor density, synthesis and insertion of AChRs should presumably be sufficiently rapid to replace both the RTOs and the stable receptors. We have tested this prediction by blocking pre-existing AChRs in the mouse sternomastoid muscle with alpha-bungarotoxin (alpha-BuTx), and monitoring the subsequent appearance of 'new' junctional AChRs at intervals of 3 h to 20 days by labeling them with 125I-alpha-BuTx. The results show that new receptors were initially inserted rapidly (16% at 24 h and 28% at 48 h). The rate of increase of 'new' 125I-alpha-BuTx binding sites gradually slowed down during the remainder of the time period studied. Control observations excluded possible artifacts of the experimental procedure including incomplete blockade of AChRs, dissociation of toxin-receptor complexes, or experimentally induced alteration of receptor synthesis. The present demonstration of rapid synthesis and incorporation of AChRs at innervated neuromuscular junctions provides support for the concept of a subpopulation of rapidly turned over AChRs. The RTOs may serve as precursors for the larger population of stable receptors and have an important role in the metabolism of the neuromuscular synapse.

  4. Neuromuscular Adaptations to Reduced Use

    NASA Technical Reports Server (NTRS)

    Ploutz-Snyder, Lori

    2009-01-01

    This viewgraph presentation reviews the studies done to reduce neuromuscular strength loss during unilateral lower limb suspension (ULLS). Since there are animals that undergo fairly long periods of muscular disuse without any or minimal muscular atrophy, there is an answer to that might be applicable to human in situations that require no muscular use to diminish the effects of muscular atrophy. Three sets of ULLS studies were reviewed indicated that muscle strength decreased more than the muscle mass. The study reviewed exercise countermeasures to combat the atrophy, including: ischemia maintained during Compound muscle action potential (CMAP), ischemia and low load exercise, Japanese kaatsu, and the potential for rehabilitation or situations where heavy loading is undesirable. Two forms of countermeasures to unloading have been successful, (1) high-load resistance training has maintained muscle mass and strength, and low load resistance training with blood flow restriction (LL(sub BFR)). The LL(sub BFR) has been shown to increase muscle mass and strength. There has been significant interest in Tourniquet training. An increase in Growth Hormone(GH) has been noted for LL(sub BFR) exercise. An experimental study with 16 subjects 8 of whom performed ULLS, and 8 of whom performed ULLS and LL(sub BFR) exercise three times per week during the ULLS. Charts show the results of the two groups, showing that performing LL(sub BFR) exercise during 30 days of ULLS can maintain muscle size and strength and even improve muscular endurance.

  5. Splicing therapy for neuromuscular disease☆

    PubMed Central

    Douglas, Andrew G.L.; Wood, Matthew J.A.

    2013-01-01

    Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) are two of the most common inherited neuromuscular diseases in humans. Both conditions are fatal and no clinically available treatments are able to significantly alter disease course in either case. However, by manipulation of pre-mRNA splicing using antisense oligonucleotides, defective transcripts from the DMD gene and from the SMN2 gene in SMA can be modified to once again produce protein and restore function. A large number of in vitro and in vivo studies have validated the applicability of this approach and an increasing number of preliminary clinical trials have either been completed or are under way. Several different oligonucleotide chemistries can be used for this purpose and various strategies are being developed to facilitate increased delivery efficiency and prolonged therapeutic effect. As these novel therapeutic compounds start to enter the clinical arena, attention must also be drawn to the question of how best to facilitate the clinical development of such personalised genetic therapies and how best to implement their provision. PMID:23631896

  6. Maintaining Optimal Surgical Conditions With Low Insufflation Pressures is Possible With Deep Neuromuscular Blockade During Laparoscopic Colorectal Surgery: A Prospective, Randomized, Double-Blind, Parallel-Group Clinical Trial.

    PubMed

    Kim, Myoung Hwa; Lee, Ki Young; Lee, Kang-Young; Min, Byung-Soh; Yoo, Young Chul

    2016-03-01

    Carbon dioxide (CO2) absorption and increased intra-abdominal pressure can adversely affect perioperative physiology and postoperative recovery. Deep muscle relaxation is known to improve the surgical conditions during laparoscopic surgery. We aimed to compare the effects of deep and moderate neuromuscular block in laparoscopic colorectal surgery, including intra-abdominal pressure. In this prospective, double-blind, parallel-group trial, 72 adult patients undergoing laparoscopic colorectal surgery were randomized using an online randomization generator to achieve either moderate (1-2 train-of-four response, n = 36) or deep (1-2 post-tetanic count, n = 36) neuromuscular block by receiving a continuous infusion of rocuronium. Adjusted intra-abdominal pressure, which was titrated by a surgeon with maintaining the operative field during pneumoperitoneum, was recorded at 5-minute intervals. Perioperative hemodynamic parameters and postoperative outcomes were assessed. Six patients from the deep and 5 from the moderate neuromuscular block group were excluded, leaving 61 for analysis. The average adjusted IAP was lower in the deep compared to the moderate neuromuscular block group (9.3 vs 12 mm Hg, P < 0.001). The postoperative pain scores (P < 0.001) and incidence of postoperative shoulder tip pain were lower, whereas gas passing time (P = 0.002) and sips of water time (P = 0.005) were shorter in the deep neuromuscular block than in the moderate neuromuscular block group. Deep neuromuscular blocking showed several benefits compared to conventional moderate neuromuscular block, including a greater intra-abdominal pressure lowering effect, whereas surgical conditions are maintained, less severe postoperative pain and faster bowel function recovery. PMID:26945393

  7. Maintaining Optimal Surgical Conditions With Low Insufflation Pressures is Possible With Deep Neuromuscular Blockade During Laparoscopic Colorectal Surgery: A Prospective, Randomized, Double-Blind, Parallel-Group Clinical Trial.

    PubMed

    Kim, Myoung Hwa; Lee, Ki Young; Lee, Kang-Young; Min, Byung-Soh; Yoo, Young Chul

    2016-03-01

    Carbon dioxide (CO2) absorption and increased intra-abdominal pressure can adversely affect perioperative physiology and postoperative recovery. Deep muscle relaxation is known to improve the surgical conditions during laparoscopic surgery. We aimed to compare the effects of deep and moderate neuromuscular block in laparoscopic colorectal surgery, including intra-abdominal pressure. In this prospective, double-blind, parallel-group trial, 72 adult patients undergoing laparoscopic colorectal surgery were randomized using an online randomization generator to achieve either moderate (1-2 train-of-four response, n = 36) or deep (1-2 post-tetanic count, n = 36) neuromuscular block by receiving a continuous infusion of rocuronium. Adjusted intra-abdominal pressure, which was titrated by a surgeon with maintaining the operative field during pneumoperitoneum, was recorded at 5-minute intervals. Perioperative hemodynamic parameters and postoperative outcomes were assessed. Six patients from the deep and 5 from the moderate neuromuscular block group were excluded, leaving 61 for analysis. The average adjusted IAP was lower in the deep compared to the moderate neuromuscular block group (9.3 vs 12 mm Hg, P < 0.001). The postoperative pain scores (P < 0.001) and incidence of postoperative shoulder tip pain were lower, whereas gas passing time (P = 0.002) and sips of water time (P = 0.005) were shorter in the deep neuromuscular block than in the moderate neuromuscular block group. Deep neuromuscular blocking showed several benefits compared to conventional moderate neuromuscular block, including a greater intra-abdominal pressure lowering effect, whereas surgical conditions are maintained, less severe postoperative pain and faster bowel function recovery.

  8. The Child Care and Development Block Grant and Child Care Grants to States under Title IV-A of the Social Security Act: A Description of Major Provisions and Issues To Consider in Implementation.

    ERIC Educational Resources Information Center

    Blank, Helen

    The Child Care and Development Block Grant (CCDBG) and Grants to States under Title IV-A of the Social Security Act for At-Risk Child Care are two recently passed federal child care bills. These bills offer states a unique opportunity to review the ways state and federal child care and early childhood programs work together to support children and…

  9. Funds Allocation and Expenditures under the Education Block Grant. A Special Issue Report from the National Study of Local Operations under Chapter 2 of the Education Consolidation and Improvement Act.

    ERIC Educational Resources Information Center

    Apling, Richard; Padilla, Christine L.

    This document presents the findings from one aspect of the National Study of Local Operations under Chapter 2 of the Education Consolidation and Improvement Act of 1981. The report examines the distribution of funds to school districts under Chapter 2, the federal education block grant. The introductory chapter reviews findings from early studies…

  10. Oseltamivir produces hypothermic and neuromuscular effects by inhibition of nicotinic acetylcholine receptor functions: comparison to procaine and bupropion.

    PubMed

    Fukushima, Akihiro; Chazono, Kaori; Hashimoto, Yuichi; Iwajima, Yui; Yamamoto, Shohei; Maeda, Yasuhiro; Ohsawa, Masahiro; Ono, Hideki

    2015-09-01

    Oseltamivir, an anti-influenza virus drug, induces marked hypothermia in normal mice. We have proposed that the hypothermic effect arises from inhibition of the nicotinic acetylcholine receptor function of sympathetic ganglion neurons which innervate the brown adipose tissue (a heat generator). It has been reported that local anesthetics inhibit nicotinic acetylcholine receptor function by acting on its ionic channels, and that bupropion, a nicotinic antagonist, induces hypothermia. In this study, we compared the effects of oseltamivir, procaine and bupropion on body temperature, cardiovascular function and neuromuscular transmission. Intraperitoneal administration of oseltamivir (100mg/kg), procaine (86.6mg/kg) and bupropion (86.7mg/kg) lowered the core body temperature of normal mice. At lower doses (10-30mg/kg oseltamivir, 8.7-26mg/kg procaine and bupropion), when administered subcutaneously, the three drugs antagonized the hypothermia induced by intraperitoneal injection of nicotine (1mg/kg). In anesthetized rats, intravenous oseltamivir (30-100mg/kg), procaine (10mg/kg) and bupropion (10mg/kg) induced hypotension and bradycardia. Oseltamivir alone (100mg/kg) did not inhibit neuromuscular twitch contraction of rats, but at 3-30mg/kg it augmented the muscle-relaxing effect of d-tubocurarine. Similar effects were observed when lower doses of procaine (10-30mg/kg) and bupropion (3-10mg/kg) were administered, suggesting that systemic administration of oseltamivir inhibits muscular nicotinic acetylcholine receptors. These results support the idea that the hypothermic effect of oseltamivir is due to its effects on sympathetic ganglia which innervate the brown adipose tissue, and suggest that oseltamivir may exert non-selective ion channel blocking effects like those of ester-type local anesthetics.

  11. Oseltamivir produces hypothermic and neuromuscular effects by inhibition of nicotinic acetylcholine receptor functions: comparison to procaine and bupropion.

    PubMed

    Fukushima, Akihiro; Chazono, Kaori; Hashimoto, Yuichi; Iwajima, Yui; Yamamoto, Shohei; Maeda, Yasuhiro; Ohsawa, Masahiro; Ono, Hideki

    2015-09-01

    Oseltamivir, an anti-influenza virus drug, induces marked hypothermia in normal mice. We have proposed that the hypothermic effect arises from inhibition of the nicotinic acetylcholine receptor function of sympathetic ganglion neurons which innervate the brown adipose tissue (a heat generator). It has been reported that local anesthetics inhibit nicotinic acetylcholine receptor function by acting on its ionic channels, and that bupropion, a nicotinic antagonist, induces hypothermia. In this study, we compared the effects of oseltamivir, procaine and bupropion on body temperature, cardiovascular function and neuromuscular transmission. Intraperitoneal administration of oseltamivir (100mg/kg), procaine (86.6mg/kg) and bupropion (86.7mg/kg) lowered the core body temperature of normal mice. At lower doses (10-30mg/kg oseltamivir, 8.7-26mg/kg procaine and bupropion), when administered subcutaneously, the three drugs antagonized the hypothermia induced by intraperitoneal injection of nicotine (1mg/kg). In anesthetized rats, intravenous oseltamivir (30-100mg/kg), procaine (10mg/kg) and bupropion (10mg/kg) induced hypotension and bradycardia. Oseltamivir alone (100mg/kg) did not inhibit neuromuscular twitch contraction of rats, but at 3-30mg/kg it augmented the muscle-relaxing effect of d-tubocurarine. Similar effects were observed when lower doses of procaine (10-30mg/kg) and bupropion (3-10mg/kg) were administered, suggesting that systemic administration of oseltamivir inhibits muscular nicotinic acetylcholine receptors. These results support the idea that the hypothermic effect of oseltamivir is due to its effects on sympathetic ganglia which innervate the brown adipose tissue, and suggest that oseltamivir may exert non-selective ion channel blocking effects like those of ester-type local anesthetics. PMID:26049014

  12. Effects of several antibiotics on the neuromuscular junction: Part II.

    PubMed

    Yamada, S; Kuno, Y; Iwanaga, H

    1986-04-01

    The effects of various kinds of antibiotics including tetracycline (TC), chloramphenicol (CP), sodium cephalothin (CET), sodium cefazolin (CEZ), colistin sulfate (CL), colistin sodium methanesulfonate (CL-M), bacitracin (BC), gramicidin HCl (GR), rifampicin sulfate (RFP) and lincomycin (LCM), on the neuromuscular junction (NMJ) were studied by in vitro and in vivo experiments. In in vitro experiments, CL and LCM exhibited a blocking effect on the NMJ in rat phrenic nerve diaphragm preparations, and GR caused a marked increase in muscle contraction. This effect was not affected by administration of eserine or CaCl2. In in vitro experiments with frog sciatica nerve and musculus sartorius preparations, CL and GR induced the appearance of endplate potentials, suggesting blockade of the NMJ. No blocking effect of other antibiotics was observed. In in vitro experiments with the preparations from Rana catesbiana frogs, TC and LCM induced a decrease in the frequency of miniature endplate potentials. In in vivo experiments with rabbit musculus tibialis anterior preparations, CL, TC and LCM exerted a blocking effect soon after administration, but GR and RFP had a late blocking effect. CL, GR, BC and RFP were found not to compete with eserine or CaCl2 in terms of the blocking effect on the NMJ. From the fact that TC did not compete with eserine but did compete with CaCl2 and with KCl as blockers at the NMJ, this blocking effect of TC seems to be due to inhibition of release of acetylcholine (ACh). The fact that LCM competes with eserine indicates that this antibiotic has the same type of action as curare on ACh receptors of the NMJ.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3486835

  13. Flightless Flies: Drosophila models of neuromuscular disease

    PubMed Central

    Lloyd, Thomas E.; Taylor, J. Paul

    2010-01-01

    The fruit fly, Drosophila melanogaster, has a long and rich history as an important model organism for biologists. In particular, study of the fruit fly has been essential to much of our fundamental understanding of the development and function of the nervous system. In recent years, studies using fruit flies have provided important insights into the pathogenesis of neurodegenerative and neuromuscular diseases. Fly models of spinal muscular atrophy, spinobulbar muscular atrophy, myotonic dystrophy, dystrophinopathies and other inherited neuromuscular diseases recapitulate many of the key pathologic features of the human disease. The ability to perform genetic screens holds promise for uncovering the molecular mechanisms of disease, and indeed, for identifying novel therapeutic targets. This review will summarize recent progress in developing fly models of neuromuscular diseases and will emphasize the contribution that Drosophila has made to our understanding of these diseases. PMID:20329357

  14. Scoliosis and the impact in neuromuscular disease.

    PubMed

    Mayer, Oscar Henry

    2015-01-01

    Scoliosis can alter respiratory mechanics by changing the orientation of the muscles and joints of the respiratory system and in severe forms can put a patient at risk of severe respiratory morbidity or respiratory failure. However, perhaps the most important factor in determining the pulmonary morbidity in scoliosis is the balance between the "load" or altered respiratory mechanics and the "pump" or the respiratory muscle strength. Therefore, scoliosis in patients with neuromuscular disease will both lead to increased "load" and a weakened "pump", an exceptionally unfortunate combination. While progressive neuromuscular disease by its nature does not respond favorably to attempts to improve respiratory muscle strength, the natural approach of early proactive management of the "load" and in the case of scoliosis a variety of different strategies have been tried with variable short term and long term results. Figuring this out requires both an understanding of the underlying pathophysiology of a particular neuromuscular condition and the available options for and timing of surgical intervention.

  15. The Human Homolog of Drosophila Headcase Acts as a Tumor Suppressor through Its Blocking Effect on the Cell Cycle in Hepatocellular Carcinoma

    PubMed Central

    Wang, Jun; Gong, Li; Zhu, Shao-Jun; Zhu, Qiao; Yao, Li; Han, Xiu-Juan; Zhang, Jia-Rui; Li, Yan-Hong; Zhang, Wei

    2015-01-01

    The molecular pathogenesis of hepatocellular carcinoma (HCC) is heterogeneous and extremely complex. Thus, for individual molecular targeted therapy, novel molecular markers are needed. The abnormal expression of the human homolog of Drosophila headcase (HECA homo) has been found in pancreatic, colorectal, and oral squamous cell carcinoma. Studies of oral squamous cell carcinoma have also demonstrated that the HECA homo protein can be negatively controlled by the Wnt-pathway and transcription factor 4 (TCF4) and can slow cell division by interacting with cyclins and CDKs. However, the role of HECA in HCC has not been reported elsewhere. Here, immunohistochemical analysis revealed that the downregulation of HECA homo protein occurred in 71.0% (66/93) of HCC cases and was positively correlated with a poorly differentiated grade, high serum AFP level, liver cirrhosis and large tumor size. The expression of HECA homo was detected in five live cell lines. In vitro, the overexpression of HECA homo in HepG2, Huh-7 and MHCC-97H cells could inhibit cell proliferation and colony formation and induce G1 phase arrest. In contrast, the downregulation of HECA homo could promote cell proliferation, colony formation and the cell cycle process. However, neither the overexpression nor downregulation of HECA homo in the three cell lines could affect cell migration or invasion. Collectively, HECA homo is regularly expressed in normal live cells, and the HECA homo protein level is heterogeneously altered in HCC, but the downregulation of HECA homo is more common and positively correlated with several malignant phenotypes. The HECA homo protein can slow cell proliferation to some extent primarily through its blocking effect on the cell cycle. Hence, the HECA homo protein may act as a tumor suppressor in HCC and might be a potential molecular marker for diagnostic classification and targeted therapy in HCC. PMID:26356417

  16. Heart Block

    MedlinePlus

    ... Block Explore Heart Block What Is... Electrical System & EKG Results Types Causes Who Is at Risk Signs & ... heart block. Doctors use a test called an EKG (electrocardiogram) to help diagnose heart block. This test ...

  17. Neuromuscular disorders and sleep in critically ill patients.

    PubMed

    Irfan, Muna; Selim, Bernardo; Rabinstein, Alejandro A; St Louis, Erik K

    2015-07-01

    Sleep-disordered breathing (SDB) is a frequent presenting manifestation of neuromuscular disorders and can lead to significant morbidity and mortality. If not recognized and addressed early in the clinical course, SDB can lead to clinical deterioration with respiratory failure. The pathophysiologic basis of SDB in neuromuscular disorders, clinical features encountered in specific neuromuscular diseases, and diagnostic and management strategies for SDB in neuromuscular patients in the critical care setting are reviewed. Noninvasive positive pressure ventilation has been a crucial advance in critical care management, improving sleep quality and often preventing or delaying mechanical ventilation and improving survival in neuromuscular patients.

  18. Neuromuscular Disorders and Sleep in Critically Ill Patients

    PubMed Central

    Irfan, Muna; Selim, Bernardo; Rabinstein, Alejandro A.

    2016-01-01

    Synopsis Sleep-disordered breathing (SDB) is a frequent presenting manifestation of neuromuscular disorders and can lead to significant morbidity and mortality. If not promptly recognized and addressed early in the clinical course, SDB can lead to clinical deterioration with respiratory failure. In this article, we review the pathophysiologic basis of SDB in neuromuscular disorders, clinical features encountered in specific neuromuscular diseases, and diagnostic and management strategies for SDB in neuromuscular patients in the critical care setting. Non-invasive positive pressure ventilation (NIPV) has been a crucial advance in critical care management, improving sleep quality and often preventing or delaying mechanical ventilation and improving survival in neuromuscular patients. PMID:26118919

  19. [Anesthetic Management of a Patient with Facioscapulohumeral Muscular Dystrophy: Importance of Monitoring Neuromuscular Function at Multiple Sites].

    PubMed

    Matsui, Shuhei; Tanaka, Satoshi; Kiyosawa, Kenkichi; Tanaka, Toshiyuki; Kawamata, Mikito

    2015-12-01

    A 39-year-old female with facioscapulohumeral muscular dystrophy (FSHD) was scheduled for thoracoscopic resection of an anterior mediastinal tumor. She had slowly progressive weakness and atrophy in the fascial and shoulder girdle muscles. General anesthesia was induced and maintained with propofol, remifentanil, and fentanyl combined with thoracic paravertebral block. Rocuronium-induced neuromuscular blockade was evaluated with acceleromyography at the corrugator supercilii, masseter, and adductor pollicis muscles. There was no reaction at the atrophic corrugator supercilii muscle in response to train-of-four (TOF) stimulation even before rocuronium administration. In contrast twitch responses at the masseter and adductor pollicis muscles to TOF stimulation could be evoked and the duration of action of rocuronium was found to be similar to that of the normal population. The perioperative course was uneventful. Neuromuscular monitoring sites should be carefully selected in FSHD patients because of possible inability to monitor neuromuscular function at the atrophic muscles. PMID:26790332

  20. Electrodiagnosis of disorders of neuromuscular transmission.

    PubMed

    Howard, James F

    2013-02-01

    This article reviews the use of electrodiagnostic testing in disorders of neuromuscular transmission and discusses the differences between various presynaptic and postsynaptic disorders. Attention is paid to quality control issues that influence the sensitivity of repetitive nerve stimulation and single fiber electromyography. Electrodiagnostic testing, when used as an extension of the clinician's history and physical examination, will provide appropriate direction in establishing the diagnosis.

  1. Dynamic Flexibility and Proprioceptive Neuromuscular Facilitation.

    ERIC Educational Resources Information Center

    Hardy, Lew; Jones, David

    1986-01-01

    Two experiments are described which investigated whether results obtained in studies of static flexibility tranfer to dynamic flexibility. In both experiments, subjects were assigned to a group receiving proprioceptive neuromuscular facilitation training, ballistic stretching technique training or a control group. Results are presented and…

  2. Short term modulation of trunk neuromuscular responses following spinal manipulation: a control group study

    PubMed Central

    2013-01-01

    Background Low back pain (LBP) is one of the most frequent musculoskeletal conditions in industrialized countries and its economic impact is important. Spinal manipulation therapy (SMT) is believed to be a valid approach in the treatment of both acute and chronic LBP. It has also been shown that SMT can modulate the electromyographic (EMG) activity of the paraspinal muscle. The purpose of this study was to investigate, in a group of patients with low back pain, the persistence of changes observed in trunk neuromuscular responses after a spinal manipulation (SMT). Methods Sixty adult participants with LBP performed a block of 5 flexion-extension movements. Participants in the experimental group (n=30) received lumbar SMT whereas participants in the control group (n=30) were positioned similarly for the treatment but did not receive SMT. Blocks of flexion-extension movements were repeated immediately after the manipulation as well as 5 and 30 minutes after SMT (or control position). EMG activity of paraspinal muscles was recorded at L2 and L5 level and kinematic data were collected to evaluate the lumbo-pelvic kinematics. Pain intensity was noted after each block. Normalized EMG, pain intensity and lumbo-pelvic kinematics were compared across experimental conditions. Results Participants from the control group showed a significant increase in EMG activity during the last block (30 min) of flexion-extension trials in both flexion and full-flexion phases at L2. Increase in VAS scores was also observed in the last 2 blocks (5 min and 30 min) in the control group. No significant group x time interaction was seen at L5. No significant difference was observed in the lumbo-pelvic kinematics. Conclusion Changes in trunk neuromuscular control following HVLA spinal manipulation may reduce sensitization or muscle fatigue effects related to repetitive movement. Future studies should investigate short term changes in neuromuscular components, tissue properties and clinical

  3. 2-O-substituted cyclodextrins as reversal agents for the neuromuscular blocker rocuronium bromide.

    PubMed

    Tarver, Gary J; Grove, Simon J A; Buchanan, Kirsteen; Bom, Anton; Cooke, Andrew; Rutherford, Samantha J; Zhang, Ming Qiang

    2002-06-01

    A series of secondary face modified cyclodextrins (CDs) were synthesised with the aim of constructing host molecules capable of forming host-guest complexes with neuromuscular blockers, especially with rocuronium bromide. Perfacial 2-O-substitution of gamma-CD with 4-carboxybenzyl resulted in a CD host molecule 1 that forms a 1:1 binary complex with rocuronium bromide (K(a) 6.2 x 10(5) M(-1)). The biological activities of this compound and other derivatives as reversal agents of rocuronium bromide were examined in vitro (mouse hemi-diaphragm) and in vivo (anaesthetized guinea pigs). The host molecule 1 was found to exert potent reversal activity (ED(50) 0.21 micromol/kg, iv) against rocuronium-induced neuromuscular block, and thus proved the viability of using host molecules as antidotes of a biologically active compound.

  4. [Genetic defects and disorders at the neuromuscular junction].

    PubMed

    Ohno, Kinji

    2011-07-01

    Genetic defects in molecules expressed at the neuromuscular junction (NMJ) cause congenital myasthenic syndromes (CMSs), which are characterized by muscle weakness, abnormal fatigability, amyotrophy, and minor facial anomalies. Muscle weakness mostly develops under 2 years but is also sometimes seen in adults. Mutations identified to date include (i) muscle nicotinic acetylcholine receptor (AChR) subunits, (ii) rapsyn that anchors and clusters AChRs at the neuromuscular junction, (iii) agrin that is released from the nerve terminal and induces AChR clustering by stimulating the downstream LRP4/MuSK/Dok-7/rapsyn/AChR pathway, (iv) muscle-specific kinase (MuSK) that transmits the AChR-clustering signal from agrin/LRP4 to rapsyn/AChR, (v) Dok-7 that transmits the AChR-clustering signal from agrin/LRP4/MuSK to rapsyn/AChR, (vi) skeletal muscle sodium channel type 1.4 (Nav1.4) that spreads the depolarization potential from the endplate throughout muscle fibers, (vii) collagen Q that anchors acetylcholinesterase to the synaptic basal lamina, and (viii) choline acetyltransferase that resynthesizes acetylcholine from recycled choline at the nerve terminal. In addition, mutations in the heparin sulfate proteoglycan perlecan, which binds to many molecules including collagen Q and dystroglycan, causes Schwartz-Jampel syndrome. Interestingly, mutations in LRP4 cause Cenani-Lenz syndactyly syndrome but not CMS. AChR, MuSK, and LRP4 are also targets of auto-antibodies in myasthenia gravis. In addition, molecules at the NMJ are targets of many other disease states AChRs are blocked by the snake toxin alpha-bungarotoxin and the plant poison curare. The presynaptic SNARE complex is attacked by botulinum toxin. Acetylcholinesterase is inhibited by the nerve gas sarin and by organophosphate pesticides. This review focuses on the molecular bases underlying defects of AChR, rapsyn, Nav1.4, collagen Q, and choline acetyltransferase. PMID:21747136

  5. Neuromuscular blockers—a means of palliation?

    PubMed Central

    Hawryluck, L

    2002-01-01

    As we die, our respiratory pattern is altered and we seem to gasp and struggle for each breath. Such gasping is commonly seen as a clear sign of dyspnoea and suffering by families and loved ones, however, it is unclear whether it is perceived at all by the dying person. Narcotics and sedatives do not seem to affect these gasping respirations. In this issue of the Journal of Medical Ethics, we are asked to consider whether the last gasp of a dying patient could be or, perhaps, even should be avoided by administering neuromuscular blockers to palliate dying patients. For many reasons, such as our current failure to alleviate pain and distress, stories of inadequate analgesia and sedation in critically ill paralysed patients and the inability to know the intent—whether to palliate or to euthanise—it would seem that administering neuromuscular blockers should not be ethically permissible. PMID:12042402

  6. Neuromuscular choristoma of the internal auditory meatus.

    PubMed

    Nikolaou, Georgios; Röösli, Christof; Huber, Alex; Probst, Rudolf

    2012-01-01

    Choristomas of the internal auditory meatus are exceedingly rare tumors. In most cases, neuromuscular choristomas have initially been misdiagnosed as vestibular schwannomas (VS). No known characteristics in the clinical presentation or in imaging exist distinguishing these tumors from VS, which are the most common tumors at this location [Smith et al.: AJNR Am J Neuroradiol 1997;18:327-329]. We present a case of a neuromuscular choristoma of the 8th cranial nerve that was operated because of growth demonstrated on two MRI scans 3 months apart. We were convinced that this young patient would require treatment sometime in the future, and we believed that an operation at that time had higher chances to preserve the anatomical structures. Histomorphological examination of the tumor revealed a nodular lesion with fascicular and nodular assembled smooth muscle cells, connective tissue and nerve fibers.

  7. Targeting RNA to treat neuromuscular disease.

    PubMed

    Muntoni, Francesco; Wood, Matthew J A

    2011-08-01

    The development of effective therapies for neuromuscular disorders such as Duchenne muscular dystrophy (DMD) is hampered by considerable challenges: skeletal muscle is the most abundant tissue in the body, and many neuromuscular disorders are multisystemic conditions. However, despite these barriers there has recently been substantial progress in the search for novel treatments. In particular, the use of antisense oligonucleotides, which are designed to target RNA and modulate pre-mRNA splicing to restore functional protein isoforms or directly inhibit the toxic effects of pathogenic RNAs, offers great promise and these approaches are now being tested in the clinic. Here, we review recent advances in the development of such antisense oligonucleotides and other promising novel approaches, including the induction of readthrough nonsense mutations.

  8. Neuromuscular Electrical Stimulation for Skeletal Muscle Function

    PubMed Central

    Doucet, Barbara M.; Lam, Amy; Griffin, Lisa

    2012-01-01

    Lack of neural innervation due to neurological damage renders muscle unable to produce force. Use of electrical stimulation is a medium in which investigators have tried to find a way to restore movement and the ability to perform activities of daily living. Different methods of applying electrical current to modify neuromuscular activity are electrical stimulation (ES), neuromuscular electrical stimulation (NMES), transcutaneous electrical nerve stimulation (TENS), and functional electrical stimulation (FES). This review covers the aspects of electrical stimulation used for rehabilitation and functional purposes. Discussed are the various parameters of electrical stimulation, including frequency, pulse width/duration, duty cycle, intensity/amplitude, ramp time, pulse pattern, program duration, program frequency, and muscle group activated, and how they affect fatigue in the stimulated muscle. PMID:22737049

  9. Diurnal hypercapnia in patients with neuromuscular disease.

    PubMed

    Panitch, Howard B

    2010-03-01

    Subjects with progressive neuromuscular diseases undergo a typical sequence of respiratory compromise, leading from normal unassisted gas exchange to nocturnal hypoventilation with normal daytime gas exchange, and eventually to respiratory failure requiring continuous ventilatory support. Several different abnormalities in respiratory pump function have been described to explain the development of respiratory failure in subjects with neuromuscular weakness. Early in the progression of respiratory failure, the use of nocturnal assisted ventilation can reverse both night- and day-time hypercapnia. Eventually, however, diurnal hypercapnia will persist despite correction of nocturnal hypoventilation. The likely beneficial effects of mechanical ventilatory support include resting fatigue-prone respiratory muscles and resetting of the central chemoreceptors to PaCO(2). Recent experience shows that select patients who require daytime ventilation can be supported with non-invasive ventilation continuously to correct gas exchange abnormalities while avoiding detrimental aspects of tracheostomy placement.

  10. [Obturator nerve block in transurethral surgery].

    PubMed

    Rubial Alvarez, M; Molins Gauna, N; Rubio Pascual, P; Martín Bermejo, P; Pamplona Casamayor, M

    1989-01-01

    The obturator nerve passes in close proximity to the bladder as it courses through the pelvis. During transurethral operations, resection may result in stimulation of the obturator nerve, causing violent adductor contraction. Bladder perforation and incomplete tumor resection are the most important complications. All techniques proposed since transurethral surgery began, until nowadays are reviewed: neuromuscular blockade, electric circuit modifications, transparietal endoscopic blockade, periprostatic and subvesical infiltration, obturator nerve blockade and the "3 in 1 block" described by Winnie. Practical advices are proposed finally.

  11. Neuromuscular rehabilitation and electrodiagnosis. 4. Specialized neuropathy.

    PubMed

    Agre, J C; Sliwa, J A

    2000-03-01

    This self-directed learning module briefly highlights the differential diagnosis for acute weakness in patients with acute respiratory failure requiring prolonged mechanical ventilation. It is part of the chapter on neuromuscular rehabilitation and electrodiagnosis in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article includes a discussion on the role of exercise in the treatment of patients with the late effects of poliomyelitis or with acute inflammatory demyelinating polyradiculoneuropathy.

  12. Neuromuscular control of prey capture in frogs.

    PubMed Central

    Nishikawa, K C

    1999-01-01

    While retaining a feeding apparatus that is surprisingly conservative morphologically, frogs as a group exhibit great variability in the biomechanics of tongue protraction during prey capture, which in turn is related to differences in neuromuscular control. In this paper, I address the following three questions. (1) How do frog tongues differ biomechanically? (2) What anatomical and physiological differences are responsible? (3) How is biomechanics related to mechanisms of neuromuscular control? Frog species use three non-exclusive mechanisms to protract their tongues during feeding: (i) mechanical pulling, in which the tongue shortens as its muscles contract during protraction; (ii) inertial elongation, in which the tongue lengthens under inertial and muscular loading; and (iii) hydrostatic elongation, in which the tongue lengthens under constraints imposed by the constant volume of a muscular hydrostat. Major differences among these functional types include (i) the amount and orientation of collagen fibres associated with the tongue muscles and the mechanical properties that this connective tissue confers to the tongue as a whole; and (ii) the transfer of intertia from the opening jaws to the tongue, which probably involves a catch mechanism that increases the acceleration achieved during mouth opening. The mechanisms of tongue protraction differ in the types of neural mechanisms that are used to control tongue movements, particularly in the relative importance of feed-forward versus feedback control, in requirements for precise interjoint coordination, in the size and number of motor units, and in the afferent pathways that are involved in coordinating tongue and jaw movements. Evolution of biomechanics and neuromuscular control of frog tongues provides an example in which neuromuscular control is finely tuned to the biomechanical constraints and opportunities provided by differences in morphological design among species. PMID:10382226

  13. Neuromuscular Diseases Associated with HIV-1 Infection

    PubMed Central

    Robinson-Papp, Jessica; Simpson, David M.

    2010-01-01

    Neuromuscular disorders are common in HIV, occurring at all stages of disease and affecting all parts of the peripheral nervous system. These disorders have diverse etiologies including HIV itself, immune suppression and dysregulation, co-morbid illnesses and infections, and side effects of medications. In this article, we review the following HIV-associated conditions: distal symmetric polyneuropathy, inflammatory demyelinating polyneuropathy, mononeuropathy, mononeuropathy multiplex, autonomic neuropathy, progressive polyradiculopathy due to cytomegalovirus, herpes zoster, myopathy and other rarer disorders. PMID:19771594

  14. Neuromuscular adaptation to actual and simulated weightlessness

    NASA Technical Reports Server (NTRS)

    Edgerton, V. R.; Roy, R. R.

    1994-01-01

    The chronic "unloading" of the neuromuscular system during spaceflight has detrimental functional and morphological effects. Changes in the metabolic and mechanical properties of the musculature can be attributed largely to the loss of muscle protein and the alteration in the relative proportion of the proteins in skeletal muscle, particularly in the muscles that have an antigravity function under normal loading conditions. These adaptations could result in decrements in the performance of routine or specialized motor tasks, both of which may be critical for survival in an altered gravitational field, i.e., during spaceflight and during return to 1 G. For example, the loss in extensor muscle mass requires a higher percentage of recruitment of the motor pools for any specific motor task. Thus, a faster rate of fatigue will occur in the activated muscles. These consequences emphasize the importance of developing techniques for minimizing muscle loss during spaceflight, at least in preparation for the return to 1 G after spaceflight. New insights into the complexity and the interactive elements that contribute to the neuromuscular adaptations to space have been gained from studies of the role of exercise and/or growth factors as countermeasures of atrophy. The present chapter illustrates the inevitable interactive effects of neural and muscular systems in adapting to space. It also describes the considerable progress that has been made toward the goal of minimizing the functional impact of the stimuli that induce the neuromuscular adaptations to space.

  15. THE ANALYSIS OF NEUROMUSCULAR MECHANISMS IN CHITON.

    PubMed

    Crozier, W J

    1920-07-20

    1. The degree of curvature of the body and of the girdle of a Chiton is determined by the activity of antagonistic muscle groups. At a certain, early stage in the strychninization of a Chiton the reciprocal inhibition involved in the natural use of these muscle groups is reversed, such that extensor muscles, rather than, as normally, flexor muscles, contract as the result of stimulation. This condition involves a reversal, under strychnine, of the normally positive stereotropism of the foot, and of the usual response of the mollusk to an increased illumination of its ventral surface. Strychnine reversal of this character is not a matter of the relative strength of the opposed muscle groups, for the flexor muscles are the more powerful and are the ones always shortened in tetanic contraction. 2. Nicotine, in contrast to strychnine, primarily induces contraction of flexor muscles. Its effects, moreover, are in a degree selective, being notably exerted on "cerebral" nervous structures. Curare is devoid of characteristic action on the neuromuscular responses of Chiton. 3. The chemical organization of the neuromuscular organs of Chiton, as far as revealed by these tests, corresponds to a more simple condition than is inferred for gastropods. In particular, the behavior with respect to curare resembles more that of the neuromuscular apparatus of flatworms.

  16. Neuromuscular Disease in the Neurointensive Care Unit.

    PubMed

    Crespo, Veronica; James, Michael L Luke

    2016-09-01

    Neuromuscular diseases are syndromic disorders that affect nerve, muscle, and/or neuromuscular junction. Knowledge about the management of these diseases is required for anesthesiologists, because these may frequently be encountered in the intensive care unit, operating room, and other settings. The challenges and advances in management for some of the neuromuscular diseases most commonly encountered in the operating room and neurointensive care unit are reviewed. PMID:27521200

  17. LRP4 is critical for neuromuscular junction maintenance.

    PubMed

    Barik, Arnab; Lu, Yisheng; Sathyamurthy, Anupama; Bowman, Andrew; Shen, Chengyong; Li, Lei; Xiong, Wen-cheng; Mei, Lin

    2014-10-15

    The neuromuscular junction (NMJ) is a synapse between motor neurons and skeletal muscle fibers, and is critical for control of muscle contraction. Its formation requires neuronal agrin that acts by binding to LRP4 to stimulate MuSK. Mutations have been identified in agrin, MuSK, and LRP4 in patients with congenital myasthenic syndrome, and patients with myasthenia gravis develop antibodies against agrin, LRP4, and MuSK. However, it remains unclear whether the agrin signaling pathway is critical for NMJ maintenance because null mutation of any of the three genes is perinatal lethal. In this study, we generated imKO mice, a mutant strain whose LRP4 gene can be deleted in muscles by doxycycline (Dox) treatment. Ablation of the LRP4 gene in adult muscle enabled studies of its role in NMJ maintenance. We demonstrate that Dox treatment of P30 mice reduced muscle strength and compound muscle action potentials. AChR clusters became fragmented with diminished junctional folds and synaptic vesicles. The amplitude and frequency of miniature endplate potentials were reduced, indicating impaired neuromuscular transmission and providing cellular mechanisms of adult LRP4 deficiency. We showed that LRP4 ablation led to the loss of synaptic agrin and the 90 kDa fragments, which occurred ahead of other prejunctional and postjunctional components, suggesting that LRP4 may regulate the stability of synaptic agrin. These observations demonstrate that LRP4 is essential for maintaining the structural and functional integrity of the NMJ and that loss of muscle LRP4 in adulthood alone is sufficient to cause myasthenic symptoms. PMID:25319686

  18. LRP4 Is Critical for Neuromuscular Junction Maintenance

    PubMed Central

    Barik, Arnab; Lu, Yisheng; Sathyamurthy, Anupama; Bowman, Andrew; Shen, Chengyong; Li, Lei; Xiong, Wen-cheng

    2014-01-01

    The neuromuscular junction (NMJ) is a synapse between motor neurons and skeletal muscle fibers, and is critical for control of muscle contraction. Its formation requires neuronal agrin that acts by binding to LRP4 to stimulate MuSK. Mutations have been identified in agrin, MuSK, and LRP4 in patients with congenital myasthenic syndrome, and patients with myasthenia gravis develop antibodies against agrin, LRP4, and MuSK. However, it remains unclear whether the agrin signaling pathway is critical for NMJ maintenance because null mutation of any of the three genes is perinatal lethal. In this study, we generated imKO mice, a mutant strain whose LRP4 gene can be deleted in muscles by doxycycline (Dox) treatment. Ablation of the LRP4 gene in adult muscle enabled studies of its role in NMJ maintenance. We demonstrate that Dox treatment of P30 mice reduced muscle strength and compound muscle action potentials. AChR clusters became fragmented with diminished junctional folds and synaptic vesicles. The amplitude and frequency of miniature endplate potentials were reduced, indicating impaired neuromuscular transmission and providing cellular mechanisms of adult LRP4 deficiency. We showed that LRP4 ablation led to the loss of synaptic agrin and the 90 kDa fragments, which occurred ahead of other prejunctional and postjunctional components, suggesting that LRP4 may regulate the stability of synaptic agrin. These observations demonstrate that LRP4 is essential for maintaining the structural and functional integrity of the NMJ and that loss of muscle LRP4 in adulthood alone is sufficient to cause myasthenic symptoms. PMID:25319686

  19. A Markov computer simulation model of the economics of neuromuscular blockade in patients with acute respiratory distress syndrome

    PubMed Central

    Macario, Alex; Chow, John L; Dexter, Franklin

    2006-01-01

    Background Management of acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) is clinically challenging and costly. Neuromuscular blocking agents may facilitate mechanical ventilation and improve oxygenation, but may result in prolonged recovery of neuromuscular function and acute quadriplegic myopathy syndrome (AQMS). The goal of this study was to address a hypothetical question via computer modeling: Would a reduction in intubation time of 6 hours and/or a reduction in the incidence of AQMS from 25% to 21%, provide enough benefit to justify a drug with an additional expenditure of $267 (the difference in acquisition cost between a generic and brand name neuromuscular blocker)? Methods The base case was a 55 year-old man in the ICU with ARDS who receives neuromuscular blockade for 3.5 days. A Markov model was designed with hypothetical patients in 1 of 6 mutually exclusive health states: ICU-intubated, ICU-extubated, hospital ward, long-term care, home, or death, over a period of 6 months. The net monetary benefit was computed. Results Our computer simulation modeling predicted the mean cost for ARDS patients receiving standard care for 6 months to be $62,238 (5% – 95% percentiles $42,259 – $83,766), with an overall 6-month mortality of 39%. Assuming a ceiling ratio of $35,000, even if a drug (that cost $267 more) hypothetically reduced AQMS from 25% to 21% and decreased intubation time by 6 hours, the net monetary benefit would only equal $137. Conclusion ARDS patients receiving a neuromuscular blocker have a high mortality, and unpredictable outcome, which results in large variability in costs per case. If a patient dies, there is no benefit to any drug that reduces ventilation time or AQMS incidence. A prospective, randomized pharmacoeconomic study of neuromuscular blockers in the ICU to asses AQMS or intubation times is impractical because of the highly variable clinical course of patients with ARDS. PMID:16539706

  20. Studies on neuromuscular blockade by boldine in the mouse phrenic nerve-diaphragm.

    PubMed

    Kang, J J; Cheng, Y W; Fu, W M

    1998-02-01

    The effects of boldine [(S)-2,9-dihydroxyl-1,10-dimethoxy-aporphine], a major alkaloid in the leaves and bark of Boldo (Peumus boldus Mol.), on neuromuscular transmission were studied using a muscle phrenic-nerve diaphragm preparation. Boldine at concentrations lower than 200 microM preferentially inhibited, after an initial period of twitch augmentation, the nerve-evoked twitches of the mouse diaphragm and left the muscle-evoked twitches unaffected. The twitch inhibition could be restored by neostigmine or washout with Krebs solution. The twitches evoked indirectly and directly were both augmented initially, suggesting that the twitch augmentation induced by boldine was myogenic. Boldine inhibited the acetylcholine-induced contraction of denervated diaphragm dose-dependently with an IC50 value of 13.5 microM. At 50 microM, boldine specifically inhibited the amplitude of the miniature end plate potential. In addition, boldine was similar to d-tubocurarine in its action to reverse the neuromuscular blocking action of alpha-bungarotoxin. These results showed that the neuromuscular blockade by boldine on isolated mouse phrenic-nerve diaphragm might be due to its direct interaction with the postsynaptic nicotinic acetylcholine receptor. PMID:9541284

  1. Rapid synthesis of acetylcholine receptors at neuromuscular junctions. (Reannouncement with new availability information)

    SciTech Connect

    Ramsay, D.A.; Drachman, D.B.; Pestronk, A.

    1988-12-31

    The rate of acetylcholine receptor (AChR) degradation in mature, innervated mammalian neuromuscular junctions has recently been shown to be biphasic; up to 20% are rapidly turned over whereas the remainder are lost more slowly. In order to maintain normal junctional receptor density, synthesis and insertion of AChRs should presumably be sufficiently rapid to replace both the RTOs and the stable receptors. The authors have tested this prediction by blocking pre-existing AChRs in the mouse sternomastoid muscle with alpha bungarotoxin and monitoring the subsequent appearance of new junctional AChRs at intervals of 3 h to 20 days by labelling them. The results show that new receptors were initially inserted rapidly. The rate of increase of new binding sites gradually slowed down during the remainder of the time period studied. Control observations excluded possible artifacts of the experimental procedure including incomplete blockade of AChRs, dissociation of toxin receptor complexes, or experimentally induced alteration of receptor synthesis. The present demonstration of rapid synthesis and incorporation of AChRs at innervated neuromuscular junctions provides support for the concept of a subpopulation of rapidly turned over AChRs. The RTOs may serve as precursors for the large population of stable receptors and have an important role in the metabolism of the neuromuscular synapse.

  2. Conservative treatment of neuromuscular scoliosis in adult tetraplegia: a case report.

    PubMed

    Hastings, Jennifer D; Dickson, Julie; Tracy, Linsey; Baniewich, Christine; Levine, Cedar

    2014-12-01

    We report successful correction of new onset neuromuscular scoliosis without spinal surgery in a man who is 30-years post-American Spinal Injury Association Impairment Scale grade A C6 injury with new onset of left neuromuscular scoliosis (Cobb angle 45°) after a motor vehicle collision. Interventions included nightly low-load prolonged stretching (LLPS) (4h left side lying over bolster), a series of 6 botulinum toxin injections (BTIs) at 3-month intervals, and progressive seating adjustments to counteract the spinal curvature. Monthly seating adjustments included rear quadrant wedging, lateral supports, and hip blocking to promote erect and symmetrical posture. A normative Cobb angle (5°) was achieved after 8 months of treatment. Improvements in alignment were demonstrated in physical examination outcome measures at the final session and follow-up. LLPS, seating adjustments, and paraspinal BTI are nonsurgical options for treating neuromuscular scoliosis in adults with tetraplegia. Further studies are necessary to determine optimum protocols and examine generalizability of these treatment methods.

  3. Neuromuscular Effects of Common Krait (Bungarus caeruleus) Envenoming in Sri Lanka

    PubMed Central

    Silva, Anjana; Maduwage, Kalana; Sedgwick, Michael; Pilapitiya, Senaka; Weerawansa, Prasanna; Dahanayaka, Niroshana J.; Buckley, Nicholas A.; Johnston, Christopher; Siribaddana, Sisira; Isbister, Geoffrey K.

    2016-01-01

    Objective We aimed to investigate neurophysiological and clinical effects of common krait envenoming, including the time course and treatment response. Methodology Patients with definite common krait (Bungarus caeruleus) bites were recruited from a Sri Lankan hospital. All patients had serial neurological examinations and stimulated concentric needle single-fibre electromyography (sfEMG) of orbicularis oculi in hospital at 6wk and 6–9mth post-bite. Principal Findings There were 33 patients enrolled (median age 35y; 24 males). Eight did not develop neurotoxicity and had normal sfEMG. Eight had mild neurotoxicity with ptosis, normal sfEMG; six received antivenom and all recovered within 20–32h. Seventeen patients developed severe neurotoxicity with rapidly descending paralysis, from ptosis to complete ophthalmoplegia, facial, bulbar and neck weakness. All 17 received Indian polyvalent antivenom a median 3.5h post-bite (2.8–7.2h), which cleared unbound venom from blood. Despite this, the paralysis worsened requiring intubation and ventilation within 7h post-bite. sfEMG showed markedly increased jitter and neuromuscular blocks within 12h. sfEMG abnormalities gradually improved over 24h, corresponding with clinical recovery. Muscle recovery occurred in ascending order. Myotoxicity was not evident, clinically or biochemically, in any of the patients. Patients were extubated a median 96h post-bite (54–216h). On discharge, median 8 days (4–12days) post-bite, patients were clinically normal but had mild sfEMG abnormalities which persisted at 6wk post-bite. There were no clinical or neurophysiological abnormalities at 6–9mth. Conclusions Common krait envenoming causes rapid onset severe neuromuscular paralysis which takes days to recover clinically consistent with sfEMG. Subclinical neuromuscular dysfunction lasts weeks but was not permanent. Antivenom effectively cleared venom but did not prevent worsening or reverse neuromuscular paralysis. PMID:26829229

  4. Acute neuromuscular weakness associated with dengue infection

    PubMed Central

    Hira, Harmanjit Singh; Kaur, Amandeep; Shukla, Anuj

    2012-01-01

    Background: Dengue infections may present with neurological complications. Whether these are due to neuromuscular disease or electrolyte imbalance is unclear. Materials and Methods: Eighty-eight patients of dengue fever required hospitalization during epidemic in year 2010. Twelve of them presented with acute neuromuscular weakness. We enrolled them for study. Diagnosis of dengue infection based on clinical profile of patients, positive serum IgM ELISA, NS1 antigen, and sero-typing. Complete hemogram, kidney and liver functions, serum electrolytes, and creatine phosphokinase (CPK) were tested. In addition, two patients underwent nerve conduction velocity (NCV) test and electromyography. Results: Twelve patients were included in the present study. Their age was between 18 and 34 years. Fever, myalgia, and motor weakness of limbs were most common presenting symptoms. Motor weakness developed on 2nd to 4th day of illness in 11 of 12 patients. In one patient, it developed on 10th day of illness. Ten of 12 showed hypokalemia. One was of Guillain-Barré syndrome and other suffered from myositis; they underwent NCV and electromyography. Serum CPK and SGOT raised in 8 out of 12 patients. CPK of patient of myositis was 5098 IU. All of 12 patients had thrombocytopenia. WBC was in normal range. Dengue virus was isolated in three patients, and it was of serotype 1. CSF was normal in all. Within 24 hours, those with hypokalemia recovered by potassium correction. Conclusions: It was concluded that the dengue virus infection led to acute neuromuscular weakness because of hypokalemia, myositis, and Guillain-Barré syndrome. It was suggested to look for presence of hypokalemia in such patients. PMID:22346188

  5. Neuromuscular Functions on Experimental Acute Methanol Intoxication

    PubMed Central

    Moral, Ali Reşat; Çankayalı, İlkin; Sergin, Demet; Boyacılar, Özden

    2015-01-01

    Objective The incidence of accidental or suicidal ingestion of methyl alcohol is high and methyl alcohol intoxication has high mortality. Methyl alcohol intoxication causes severe neurological sequelae and appears to be a significant problem. Methyl alcohol causes acute metabolic acidosis, optic neuropathy leading to permanent blindness, respiratory failure, circulatory failure and death. It is metabolised in the liver, and its metabolite formic acid has direct toxic effects, causing oxidative stress, mitochondrial damage and increased lipid peroxidation associated with the mechanism of neurotoxicity. Methanol is known to cause acute toxicity of the central nervous system; however, the effects on peripheral neuromuscular transmission are unknown. In our study, we aimed to investigate the electrophysiological effects of experimentally induced acute methanol intoxication on neuromuscular transmission in the early period (first 24 h). Methods After approval by the Animal Experiment Ethics Committee of Ege University, the study was carried out on 10 Wistar rats, each weighing about 200 g. During electrophysiological recordings and orogastric tube insertion, the rats were anaesthetised using intra-peritoneal (IP) injection of ketamine 100 mg kg−1 and IP injection of xylazine 10 mg kg−1. The rats were given 3 g kg−1 methyl alcohol by the orogastric tube. Electrophysiological measurements from the gastrocnemius muscle were compared with baseline. Results Latency measurements before and 24 h after methanol injection were 0.81±0.11 ms and 0.76±0.12 ms, respectively. CMAP amplitude measurements before and 24 h after methanol injection were 9.85±0.98 mV and 9.99±0.40 mV, respectively. CMAP duration measurements before and 24 h after methanol injection were 9.86±0.03 ms and 9.86±0.045 ms, respectively. Conclusion It was concluded that experimental methanol intoxication in the acute phase (first 24 h) did not affect neuromuscular function. PMID:27366524

  6. IPPB-assisted coughing in neuromuscular disorders.

    PubMed

    Dohna-Schwake, Christian; Ragette, Regine; Teschler, Helmut; Voit, Thomas; Mellies, Uwe

    2006-06-01

    In neuromuscular disorders, reduced peak cough flows (PCFs) are considered to increase the risk of respiratory complications such as pneumonia or chronic atelectasis. Different methods were described to improve PCF. However, these studies were primarily carried out in adults, and there is limited information regarding the use and efficacy of these methods in children with respiratory muscle weakness. The aim of this study was to investigate whether hyperinsufflation with an intermittent positive-pressure breathing (IPPB) device is effective in cough augmentation in pediatric patients. Spirometry (forced inspiratory vital capacity, FIVC; forced expiratory volume in 1 sec, FEV1), respiratory muscle pressures (peak inspiratory pressure, PIP; peak expiratory pressure, PEP), and PCF were measured in 29 schoolchildren with various neuromuscular disorders. IPPB-assisted hyperinsufflation was taught individually to increase lung volumes (maximum insufflation capacity, MIC) above FIVC. The impact of hyperinsufflation on peak cough flow was documented. In 28/29 patients, IPPB-assisted hyperinsufflation enhanced FIVC from 0.68 +/- 0.40 l to an MIC of 1.05 +/- 0.47 l (P < 0.001). Unassisted PCF was 119.0 +/- 57.7 l/min, and increased to 194.5 +/- 74.9 l/min (P < 0.001) in 27/29 patients. This effect was similar in young patients (ages 6-10 years) and older patients (aged >10 years). Augmentation of lung volumes from FIVC to MIC correlated with an increase of PCF (R = 0.42, P < 0.05). IPPB-assisted hyperinsufflation improves PCF in pediatric neuromuscular disorders. The results suggest that this technique can be used to improve clearance of airway secretions and therefore reduce respiratory morbidity in children with NMD.

  7. Neuromuscular Development and Regulation of Myosin Expression

    NASA Technical Reports Server (NTRS)

    Bodine, Sue

    1997-01-01

    The proposed experiments were designed to determine whether the absence of gravity during embryogenesis influences the postnatal development of the neuromuscular system. Further, we examined the effects of reduced gravity on hindlimb muscles of the pregnant rats. Microgravity may have short and long-term effects on the development of muscle fiber type differentiation and force producing capabilities. Microgravity will reduce muscle fiber size and cause a shift in myosin heavy chain expression from slow to fast in hindlimb muscles of the adult pregnant rats.

  8. Neuromuscular Characteristics of Endurance--And Power-Trained Athletes

    ERIC Educational Resources Information Center

    Koceja, David M.; Davison, Edwin; Robertson, Christopher T.

    2004-01-01

    In response to chronic physical training, the human neuromuscular system undergoes significant and specific adaptations. More importantly, these influences are the result of the type and quantity of physical activity. One of the simplest neuromuscular mechanisms is the spinal stretch reflex. The reflex system was previously viewed as inflexible,…

  9. Motoneuron and sensory neuron plasticity to varying neuromuscular activity levels

    NASA Technical Reports Server (NTRS)

    Ishihara, Akihiko; Roy, Roland R.; Ohira, Yoshinobu; Edgerton, V. Reggie

    2002-01-01

    The size and phenotypic properties of the neural and muscular elements of the neuromuscular unit are matched under normal conditions. When subjected to chronic decreases or increases in neuromuscular activity, however, the adaptations in these properties are much more limited in the neural compared with the muscular elements.

  10. 21 CFR 882.5810 - External functional neuromuscular stimulator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false External functional neuromuscular stimulator. 882.5810 Section 882.5810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... External functional neuromuscular stimulator. (a) Identification. An external functional...

  11. 21 CFR 882.5810 - External functional neuromuscular stimulator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false External functional neuromuscular stimulator. 882.5810 Section 882.5810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... External functional neuromuscular stimulator. (a) Identification. An external functional...

  12. Recent achievements in restorative neurology: Progressive neuromuscular diseases

    SciTech Connect

    Dimitrijevic, M.R.; Kakulas, B.A.; Vrbova, G.

    1986-01-01

    This book contains 27 chapters. Some of the chapter titles are: Computed Tomography of Muscles in Neuromuscular Disease; Mapping the Genes for Muscular Dystrophy; Trophic Factors and Motor Neuron Development; Size of Motor Units and Firing Rate in Muscular Dystrophy; Restorative Possibilities in Relation to the Pathology of Progressive Neuromuscular Disease; and An Approach to the Pathogenesis of some Congenital Myopathies.

  13. Population Blocks.

    ERIC Educational Resources Information Center

    Smith, Martin H.

    1992-01-01

    Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining…

  14. LDL-receptor-related protein 4 is crucial for formation of the neuromuscular junction.

    PubMed

    Weatherbee, Scott D; Anderson, Kathryn V; Niswander, Lee A

    2006-12-01

    Low-density lipoprotein receptor-related protein 4 (Lrp4) is a member of a family of structurally related, single-pass transmembrane proteins that carry out a variety of functions in development and physiology, including signal transduction and receptor-mediated endocytosis. Lrp4 is expressed in multiple tissues in the mouse, and is important for the proper development and morphogenesis of limbs, ectodermal organs, lungs and kidneys. We show that Lrp4 is also expressed in the post-synaptic endplate region of muscles and is required to form neuromuscular synapses. Lrp4-mutant mice die at birth with defects in both presynaptic and postsynaptic differentiation, including aberrant motor axon growth and branching, a lack of acetylcholine receptor and postsynaptic protein clustering, and a failure to express postsynaptic genes selectively by myofiber synaptic nuclei. Our data show that Lrp4 is required during the earliest events in postsynaptic neuromuscular junction (NMJ) formation and suggest that it acts in the early, nerveindependent steps of NMJ assembly. The identification of Lrp4 as a crucial factor for NMJ formation may have implications for human neuromuscular diseases such as myasthenia syndromes. PMID:17119023

  15. Neuromuscular Dysfunction in Experimental Sepsis and Glutamine

    PubMed Central

    Çankayalı, İlkin; Boyacılar, Özden; Demirağ, Kubilay; Uyar, Mehmet; Moral, Ali Reşat

    2016-01-01

    Background: Electrophysiological studies show that critical illness polyneuromyopathy appears in the early stage of sepsis before the manifestation of clinical findings. The metabolic response observed during sepsis causes glutamine to become a relative essential amino acid. Aims: We aimed to assess the changes in neuromuscular transmission in the early stage of sepsis after glutamine supplementation. Study Design: Animal experimentation. Methods: Twenty male Sprague-Dawley rats were randomized into two groups. Rats in both groups were given normal feeding for one week. In the study group, 1 g/kg/day glutamine was added to normal feeding by feeding tube for one week. Cecal ligation and perforation (CLP) surgery was performed at the end of one week. Before and 24 hours after CLP, compound muscle action potentials were recorded from the gastrocnemius muscle. Results: Latency measurements before and 24 hours after CLP were 0.68±0.05 ms and 0.80±0.09 ms in the control group and 0.69±0.07 ms and 0.73±0.07 ms in the study group (p<0.05). Conclusion: Since enteral glutamine prevented compound muscle action potentials (CMAP) latency prolongation in the early phase of sepsis, it was concluded that enteral glutamine replacement might be promising in the prevention of neuromuscular dysfunction in sepsis; however, further studies are required. PMID:27308070

  16. Neuromuscular imaging in inherited muscle diseases

    PubMed Central

    Kley, Rudolf A.; Fischer, Dirk

    2010-01-01

    Driven by increasing numbers of newly identified genetic defects and new insights into the field of inherited muscle diseases, neuromuscular imaging in general and magnetic resonance imaging (MRI) in particular are increasingly being used to characterise the severity and pattern of muscle involvement. Although muscle biopsy is still the gold standard for the establishment of the definitive diagnosis, muscular imaging is an important diagnostic tool for the detection and quantification of dystrophic changes during the clinical workup of patients with hereditary muscle diseases. MRI is frequently used to describe muscle involvement patterns, which aids in narrowing of the differential diagnosis and distinguishing between dystrophic and non-dystrophic diseases. Recent work has demonstrated the usefulness of muscle imaging for the detection of specific congenital myopathies, mainly for the identification of the underlying genetic defect in core and centronuclear myopathies. Muscle imaging demonstrates characteristic patterns, which can be helpful for the differentiation of individual limb girdle muscular dystrophies. The aim of this review is to give a comprehensive overview of current methods and applications as well as future perspectives in the field of neuromuscular imaging in inherited muscle diseases. We also provide diagnostic algorithms that might guide us through the differential diagnosis in hereditary myopathies. PMID:20422195

  17. Neuromuscular disruption with ultrashort electrical pulses

    NASA Astrophysics Data System (ADS)

    Pakhomov, Andrei; Kolb, Juergen F.; Joshi, Ravindra P.; Schoenbach, Karl H.; Dayton, Thomas; Comeaux, James; Ashmore, John; Beason, Charles

    2006-05-01

    Experimental studies on single cells have shown that application of pulsed voltages, with submicrosecond pulse duration and an electric field on the order of 10 kV/cm, causes sudden alterations in the intracellular free calcium concentration, followed by immobilization of the cell. In order to examine electrical stimulation and incapacitation with such ultrashort pulses, experiments on anesthetized rats have been performed. The effect of single, 450 nanosecond monopolar pulses have been compared with that of single pulses with multi-microsecond duration (TASER pulses). Two conditions were explored: 1. the ability to elicit a muscle twitch, and, 2. the ability to suppress voluntary movement by using nanosecond pulses. The second condition is relevant for neuromuscular incapacitation. The preliminary results indicate that for stimulation microsecond pulses are advantageous over nanosecond pulses, whereas for incapacitation, the opposite seems to apply. The stimulation effects seem to scale with electrical charge, whereas the disruption effects don't follow a simple scaling law. The increase in intensity (time of incapacitation) for a given pulse duration, is increasing with electrical energy, but is more efficient for nanosecond than for microsecond pulses. This indicates different cellular mechanisms for incapacitation, most likely subcellular processes, which have been shown to become increasingly important when the pulse duration is shortened into the nanosecond range. If further studies can confirm these initial results, consequences of reduced pulse duration are a reduction in weight and volume of the pulse delivery system, and likely, because of the lower required energy for neuromuscular incapacitation, reduced safety risks.

  18. Activity-dependent degeneration of axotomized neuromuscular synapses in WldS mice

    PubMed Central

    Brown, R.; Hynes-Allen, A.; Swan, A.J.; Dissanayake, K.N.; Gillingwater, T.H.; Ribchester, R.R.

    2015-01-01

    Activity and disuse of synapses are thought to influence progression of several neurodegenerative diseases in which synaptic degeneration is an early sign. Here we tested whether stimulation or disuse renders neuromuscular synapses more or less vulnerable to degeneration, using axotomy as a robust trigger. We took advantage of the slow synaptic degeneration phenotype of axotomized neuromuscular junctions in flexor digitorum brevis (FDB) and deep lumbrical (DL) muscles of Wallerian degeneration-Slow (WldS) mutant mice. First, we maintained ex vivo FDB and DL nerve-muscle explants at 32 °C for up to 48 h. About 90% of fibers from WldS mice remained innervated, compared with about 36% in wild-type muscles at the 24-h checkpoint. Periodic high-frequency nerve stimulation (100 Hz: 1 s/100 s) reduced synaptic protection in WldS preparations by about 50%. This effect was abolished in reduced Ca2+ solutions. Next, we assayed FDB and DL innervation after 7 days of complete tetrodotoxin (TTX)-block of sciatic nerve conduction in vivo, followed by tibial nerve axotomy. Five days later, only about 9% of motor endplates remained innervated in the paralyzed muscles, compared with about 50% in 5 day-axotomized muscles from saline-control-treated WldS mice with no conditioning nerve block. Finally, we gave mice access to running wheels for up to 4 weeks prior to axotomy. Surprisingly, exercising WldS mice ad libitum for 4 weeks increased about twofold the amount of subsequent axotomy-induced synaptic degeneration. Together, the data suggest that vulnerability of mature neuromuscular synapses to axotomy, a potent neurodegenerative trigger, may be enhanced bimodally, either by disuse or by hyperactivity. PMID:25617654

  19. Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons

    PubMed Central

    Lee, Young il; Mikesh, Michelle; Smith, Ian; Rimer, Mendell; Thompson, Wesley

    2011-01-01

    A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precedes the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any significant impairment in neuromuscular transmission, even when animals were maintained up to 5 days longer via a supplementary diet. However, the muscles were clearly weaker, generating less than half their normal tension. Weakness in 3 muscles examined in the study appears due to a severe but uniform reduction in muscle fiber size. The size reduction results from a failure of muscle fibers to grow during early postnatal development and, in soleus, to a reduction in number of fibers generated. Neuromuscular development is severely delayed in these mutant animals: expression of myosin heavy chain isoforms, the elimination of polyneuronal innervation, the maturation in the shape of the AChR plaque, the arrival of SCs at the junctions and their coverage of the nerve terminal, the development of junctional folds. Thus, if SMA in this particular mouse is a disease of motor neurons, it can act in a manner that does not result in their death or disconnection from their targets but nonetheless alters many aspects of neuromuscular development. PMID:21658376

  20. Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons.

    PubMed

    Lee, Young Il; Mikesh, Michelle; Smith, Ian; Rimer, Mendell; Thompson, Wesley

    2011-08-15

    A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precede the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any significant impairment in neuromuscular transmission, even when animals were maintained up to 5days longer via a supplementary diet. However, the muscles were clearly weaker, generating less than half their normal tension. Weakness in 3 muscles examined in the study appears due to a severe but uniform reduction in muscle fiber size. The size reduction results from a failure of muscle fibers to grow during early postnatal development and, in soleus, to a reduction in number of fibers generated. Neuromuscular development is severely delayed in these mutant animals: expression of myosin heavy chain isoforms, the elimination of polyneuronal innervation, the maturation in the shape of the AChR plaque, the arrival of SCs at the junctions and their coverage of the nerve terminal, the development of junctional folds. Thus, if SMA in this particular mouse is a disease of motor neurons, it can act in a manner that does not result in their death or disconnection from their targets but nonetheless alters many aspects of neuromuscular development.

  1. Surgical advances in the treatment of neuromuscular scoliosis

    PubMed Central

    Canavese, Federico; Rousset, Marie; Le Gledic, Benoit; Samba, Antoine; Dimeglio, Alain

    2014-01-01

    Neuromuscular disorders are a group of diseases affecting the neuro-musculo-skeletal system. Children with neuromuscular disorders frequently develop progressive spinal deformities with cardio-respiratory compromise in the most severe cases. The incidence of neuromuscular scoliosis is variable, inversely correlated with ambulatory abilities and with a reported risk ranging from 80% to 100% in non-ambulatory patients. As surgical and peri-operative techniques have improved, more severely affected children with complex neuromuscular deformities and considerable co-morbidities are now believed to be candidates for extensive surgery for spinal deformity. This article aimed to provide a comprehensive review of how neuromuscular spinal deformities can affect normal spine balance and how these deformities can be treated with segmental instrumentation and sub-laminar devices. Older concepts have been integrated with newer scientific data to provide the reader with a basis for better understanding of how treatment of neuromuscular scoliosis has evolved over the past few decades. Recent advances, as well as challenges that remain to be overcome, in the surgical treatment of neuromuscular curves with sub-laminar devices and in the management of post-operative infections are outlined. PMID:24829875

  2. THE ROLE OF THE NEUROMUSCULAR MEDICINE SPECIALIST AND PHYSIATRY IN THE MANAGEMENT OF NEUROMUSCULAR DISEASE

    PubMed Central

    McDonald, Craig M.; Fowler, William M.

    2012-01-01

    Synopsis The neuromuscular medicine, and physiatry specialists are key health care providers who work cooperatively with a multidisciplinary team to provide coordinated care for persons with Neuromuscular diseases (NMDs). The director or coordinator of the team must be aware of the potential issues specific to NMDs and be able to access the interventions that are the foundations for proper care in NMD. These include health maintenance and proper monitoring of disease progression and complications to provide anticipatory, preventive care and optimum management. Ultimate goals include maximizing health and functional capacities, performing medical monitoring and surveillance to inhibit and prevent complications, and promoting access and full integration into the community in order to optimize quality of life. PMID:22938874

  3. Neuromuscular ultrasound findings in polyneuropathy secondary to disulfiram.

    PubMed

    Stone, Sarah L; Cartwright, Michael S; Panea, Oana R; Vann, Ryan C; Magruder, John L; Walker, Francis O

    2014-12-01

    Disulfiram toxicity can cause multiple neurologic problems, including a reversible distal sensorimotor axonal polyneuropathy. Although electrodiagnosis and biopsy results have been described in the diagnosis and management of patients with disulfiram associated polyneuropathy, neuromuscular ultrasound findings have not been reported. The authors present a case of electrodiagnostically confirmed axonal polyneuropathy with relative sural sparing secondary to disulfiram and describe the neuromuscular ultrasound findings in this individual. Ultrasound demonstrated distal enlargement with slight side-to-side asymmetry and normal proximal cross-sectional area in the lower extremity nerves. Neuromuscular ultrasound is another diagnostic modality that may be used to assist in the diagnosis of patients with polyneuropathy secondary to disulfiram.

  4. Wnt Signaling in Neuromuscular Junction Development

    PubMed Central

    Koles, Kate

    2012-01-01

    Wnt proteins are best known for their profound roles in cell patterning, because they are required for the embryonic development of all animal species studied to date. Besides regulating cell fate, Wnt proteins are gaining increasing recognition for their roles in nervous system development and function. New studies indicate that multiple positive and negative Wnt signaling pathways take place simultaneously during the formation of vertebrate and invertebrate neuromuscular junctions. Although some Wnts are essential for the formation of NMJs, others appear to play a more modulatory role as part of multiple signaling pathways. Here we review the most recent findings regarding the function of Wnts at the NMJ from both vertebrate and invertebrate model systems. PMID:22510459

  5. Neuromuscular junction in a microfluidic device.

    PubMed

    Park, Hyun Sung; Liu, Su; McDonald, John; Thakor, Nitish; Yang, In Hong

    2013-01-01

    Malfunctions at the site of neuromuscular junction (NMJ) of post-injuries or diseases are major barriers to recovery of function. The ability to efficiently derive motor neurons (MN) from embryonic stem cells has indicated promise toward the development of new therapies in increasing functional outcomes post injury. Recent advances in micro-technologies have provided advanced culture platforms allowing compartmentalization of sub-cellular components of neurons. In this study, we combined these advances in science and technology to develop a compartmentalized in vitro NMJ model. The developed NMJ system is between mouse embryonic stem cell (mESC)-derived MNs and c2c12 myotubes cultured in a compartmentalized polydimethylsiloxane (PDMS) microfluidic device. While some functional in vitro NMJ systems have been reported, this system would further contribute to research in NMJ-related diseases by providing a system to study the site of action of NMJ aimed at improving promoting better functional recovery. PMID:24110317

  6. Load-dependent regulation of neuromuscular system

    NASA Technical Reports Server (NTRS)

    Ohira, Yoshinobu; Kawano, Fuminori; Stevens, James L.; Wang, Xiao D.; Ishihara, Akihiko

    2004-01-01

    Roles of gravitational loading, sarcomere length, and/or tension development on the electromyogram (EMG) of soleus and afferent neurogram recorded at the L5 segmental level of spinal cord were investigated during parabolic flight of a jet airplane or hindlimb suspension in conscious rats. Both EMG and neurogram levels were increased when the gravity levels were elevated from 1-G to 2-G during the parabolic flight. They were decreased when the hindlimbs were unloaded by exposure to actual microgravity or by suspension. These phenomena were related to passive shortening of muscle fibers and/or sarcomeres. Unloading-related decrease in sarcomere length was greater at the central rather than the proximal and distal regions of fibers. These activities and tension development were not detected when the mean sarcomere length was less than 2.03 micrometers. It is suggested that load-dependent regulation of neuromuscular system is related to the tension development which is influenced by sarcomere length.

  7. Neuromuscular Impairment Following Backpack Load Carriage

    PubMed Central

    Blacker, Sam D.; Fallowfield, Joanne L.; Bilzon, James L.J.; Willems, Mark E.T.

    Load Carriage using backpacks is an occupational task and can be a recreational pursuit. The aim of this study was to investigate the mechanisms responsible for changes in neuromuscular function of the m. quadriceps femoris following load carriage. The physiological responses of 10 male participants to voluntary and electrically stimulated isometric contractions were measured before and immediately after two hours of treadmill walking at 6.5 km•h −1 during level walking with no load [LW], and level walking with load carriage (25 kg backpack) [LC]. Maximal voluntary contraction force decreased by 15 ± 11 % following LC (p=0.006), with no change following LW (p=0.292). Voluntary activation decreased after LW and LC (p=0.033) with no difference between conditions (p=0.405). Doublet contraction time decreased after both LW and LC (p=0.002), with no difference between conditions (p=0.232). There were no other changes in electrically invoked doublet parameters in either condition. The 20:50 Hz ratio did not change following LW (p=0.864) but decreased from 0.88 ± 0.04 to 0.84 ± 0.04 after LC (p=0.011) indicating reduced Ca2+ release from the sarcoplasmic reticulum during excitation contraction coupling. In conclusion, two hours of load carriage carrying a 25 kg back pack caused neuromuscular impairment through a decrease in voluntary activation (i.e. central drive) and fatigue or damage to the peripheral muscle, including impairment of the excitation contraction coupling process. This may reduce physical performance and increase the risk of musculoskeletal injury. PMID:24146709

  8. Visual and tactile assessment of neuromuscular fade.

    PubMed

    Brull, S J; Silverman, D G

    1993-08-01

    The accuracy of visual and tactile assessment of the neuromuscular fade in response to train-of-four (TOF) and double-burst stimulation (DBS) were compared to assess their relative utility in the clinical setting. For each of 74 data sets with a mechanographic TOF ratio less than 0.70, an observer (blinded to the presence or degree of fade) performed visual and tactile assessments of fade in response to TOF, DBS3,3, and DBS3,2 stimuli at low current (20 and 30 mA) and high current (50 and 60 mA). For the range of mechanographic TOF ratios between 0.41 and 0.70, visual assessment failed to identify TOF, DBS3,3, and DBS3,2 fade in 46%, 18%, and 14% of cases at high current and in 23%, 5%, and 0% of cases at low current, respectively. Tactile assessments failed to identify fade in 55%, 23%, and 14% of cases at high current and in 23%, 14%, and 14% of cases at low current. Overall, the ability to detect fade was comparable for visual and tactile assessments regardless of the method of neurostimulation (P = NS with paired t-test). However, the degree of overestimation of the fade ratio (i.e., quantitative assessment) tended to be less when using tactile means; the difference achieved significance for TOF at low current and DBS3,3 at both low and high currents. We conclude that the differences between the visual and tactile means of assessment are relatively small compared to the differences among the TOF and DBS patterns of neurostimulation. Both subjective techniques are often inadequate in settings in which assurance of full recovery of neuromuscular function is critical.

  9. Explosive neuromuscular performance of males versus females.

    PubMed

    Hannah, Ricci; Minshull, Claire; Buckthorpe, Matthew W; Folland, Jonathan P

    2012-05-01

    The purpose of the study was to investigate sex-related differences in explosive muscular force production, as measured by electromechanical delay (EMD) and rate of force development (RFD), and to examine the physiological mechanisms responsible for any differences. The neuromuscular performance of untrained males (n = 20) and females (n = 20) was assessed during a series of isometric knee extension contractions; explosive and maximal voluntary efforts, as well as supramaximal evoked twitches and octets (eight pulses at 300 Hz). Evoked and voluntary EMD were determined from twitch and explosive contractions. The RFD was recorded over consecutive 50 ms time windows from force onset during evoked and explosive contractions, and normalized to maximal strength. Neuromuscular activity during explosive voluntary contractions was measured with EMG of the superficial knee extensors normalized to maximal M-wave. Muscle size (thickness) and muscle-tendon unit (MTU) stiffness were assessed using ultrasonic images of the vastus lateralis at rest and during ramped contractions. Males and females had similar evoked and voluntary EMD. Males were 33% stronger (P < 0.001) and their absolute RFD was 26-56% greater (all time points P < 0.05) compared with females. Muscle size (P < 0.001) and absolute MTU stiffness were also greater for males (P < 0.05). However, normalized RFD was similar for both sexes during the first 150 ms of the explosive voluntary contractions (P > 0.05). This was consistent with the similar normalized twitch and octet RFD, MTU stiffness and agonist EMG (all P > 0.05). When differences in maximal strength were accounted for, the evoked capacity of the knee extensors for explosive force production and the ability to utilize that capacity during explosive voluntary contractions was similar for males and females.

  10. Cardiorespiratory and neuromuscular responses to motocross riding.

    PubMed

    Konttinen, Tomi; Kyröläinen, Heikki; Häkkinen, Keijo

    2008-01-01

    The aim of the present study was to examine physiological and neuromuscular responses during motocross riding at individual maximal speed together with the riding-induced changes in maximal isometric force production. Seven A-level (group A) and 5 hobby-class (group H) motocross-riders performed a 30-minute riding test on a motocross track and maximal muscle strength and oxygen uptake (VO2max) tests in a laboratory. During the riding the mean (+/-SD) VO2 reduced in group A from 86 +/- 10% to 69 +/- 6% of the maximum (P < 0.001), whereas in group H the corresponding reduction was from 94 +/- 25% to 82 +/- 20% (P < 0.05). This relative VO2 during the riding correlated with riding speed (r = 0.70, P < 0.01). Heart rate (HR) was maintained at the level of 97 +/- 7% of its maximum in group A and at 98 +/- 3% in group H. Mean muscle activation of the lower body during riding varied between 24% and 38% of its maximum in group A and between 40% and 45% in group H. In conclusion, motocross is a sport that causes great physical stress and demands on both skill and physical capacity of the rider. Physical stress occurs as the result of handling of the bike when receiving continuous impacts in the situation requiring both aerobic and anaerobic metabolism. Our data suggest that both maximal capacity and strain during the ride should be measured to analyze the true physiological and neuromuscular demands of motocross ride. For the practice, this study strongly suggests to train not only aerobic and anaerobic capacity but also to use strength and power training for successful motocross riding. PMID:18296976

  11. Mechanism of Neuromuscular Dysfunction in Krabbe Disease

    PubMed Central

    Cantuti-Castelvetri, Ludovico; Maravilla, Erick; Marshall, Michael; Tamayo, Tammy; D'auria, Ludovic; Monge, John; Jeffries, James; Sural-Fehr, Tuba; Lopez-Rosas, Aurora; Li, Guannan; Garcia, Kelly; van Breemen, Richard; Vite, Charles; Garcia, Jesus

    2015-01-01

    The atrophy of skeletal muscles in patients with Krabbe disease is a major debilitating manifestation that worsens their quality of life and limits the clinical efficacy of current therapies. The pathogenic mechanism triggering muscle wasting is unknown. This study examined structural, functional, and metabolic changes conducive to muscle degeneration in Krabbe disease using the murine (twitcher mouse) and canine [globoid cell leukodystrophy (GLD) dog] models. Muscle degeneration, denervation, neuromuscular [neuromuscular junction (NMJ)] abnormalities, and axonal death were investigated using the reporter transgenic twitcher–Thy1.1–yellow fluorescent protein mouse. We found that mutant muscles had significant numbers of smaller-sized muscle fibers, without signs of regeneration. Muscle growth was slow and weak in twitcher mice, with decreased maximum force. The NMJ had significant levels of activated caspase-3 but limited denervation. Mutant NMJ showed reduced surface areas and lower volumes of presynaptic terminals, with depressed nerve control, increased miniature endplate potential (MEPP) amplitude, decreased MEPP frequency, and increased rise and decay rate constants. Twitcher and GLD dog muscles had significant capacity to store psychosine, the neurotoxin that accumulates in Krabbe disease. Mechanistically, muscle defects involved the inactivation of the Akt pathway and activation of the proteasome pathway. Our work indicates that muscular dysfunction in Krabbe disease is compounded by a pathogenic mechanism involving at least the failure of NMJ function, activation of proteosome degradation, and a reduction of the Akt pathway. Akt, which is key for muscle function, may constitute a novel target to complement in therapies for Krabbe disease. PMID:25632136

  12. Neuromuscular Evaluation of Trunk-Training Exercises

    PubMed Central

    Schmitz, Klaus; Denner, Achim

    2001-01-01

    Objective: To evaluate the neuromuscular activation profiles of trunk muscles in commonly used gymnastic strength exercises with a polymyographic set-up and to describe the training effects of each exercise. Design and Setting: Subjects performed 9 repetitions of each of 12 gymnastic exercises. Variations of 5 trunk flexions, 5 extensions, and 2 lateral-flexion movements were performed under standardized test conditions. Subjects: Ten healthy subjects (men and women) who were familiar with the exercises participated in the study. Measurements: We recorded surface electromyograms (EMGs) from the rectus abdominis, external oblique, rectus femoris, middle trapezius, erector spinae at T12 and L3, gluteus maximus, and semitendinosus and semimembranosus muscles. Recording of each repetition cycle was triggered by a flexible electronic goniometer attached to the trunk. The raw EMG signals were rectified, smoothed, amplitude normalized to maximal voluntary contraction (MVC), and averaged for the last 8 repetitions. Results: Pure spine-flexion exercises, such as a curl-up, produced sufficient and isolated activation (greater than 50% MVC) of the abdominal muscles. When flexion of the spine was combined with hip flexion (sit-up), the peak activation was increased. Lateral-flexion tasks targeted primarily the external oblique muscle, which demonstrated high activity in side-lying flexion tasks. Back- and hip-extension exercises, such as bridging and diagonal hip and shoulder extension, produced only moderate mean activities (less than 35% MVC) in the trunk-extensor muscles. Trunk-extension exercises with combined hip extension increased the EMG activity to 50% MVC but only at the end of the extension. Conclusions: Individual responses to each exercise varied markedly, which complicated the classification of exercise effects. However, within the limitations of the study, we found that the chosen abdominal exercises provided an effective training stimulus for the trunk

  13. Ionic Blocks

    ERIC Educational Resources Information Center

    Sevcik, Richard S.; Gamble, Rex; Martinez, Elizabet; Schultz, Linda D.; Alexander, Susan V.

    2008-01-01

    "Ionic Blocks" is a teaching tool designed to help middle school students visualize the concepts of ions, ionic compounds, and stoichiometry. It can also assist high school students in reviewing their subject mastery. Three dimensional blocks are used to represent cations and anions, with color indicating charge (positive or negative) and size…

  14. Teaching Visually Impaired Adults with a Neuromuscular Disorder.

    ERIC Educational Resources Information Center

    Williams, Susan

    1983-01-01

    The effects of four neuromuscular disorders (stroke, Parkinson's disease, Huntington's disease, and Lou Gehrig's disease) on concommitant visual impairments are considered. Rehabilitation approaches and equipment that help clients cope with the condition are described. (CL)

  15. Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

    ClinicalTrials.gov

    2015-08-24

    Spinal Muscular Atrophy; Charcot-Marie-Tooth Disease; Muscular Dystrophy; Spinal Muscular Atrophy With Respiratory Distress 1; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Disease; Peroneal Muscular Atrophy; Fragile X Syndrome

  16. 21 CFR 882.5860 - Implanted neuromuscular stimulator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Date PMA or notice of completion of PDP is required. A PMA or notice of completion of a PDP for a.... Any other implanted neuromuscular stimulator shall have an approved PMA or declared completed PDP...

  17. The potential of disease management for neuromuscular hereditary disorders.

    PubMed

    Chouinard, Maud-Christine; Gagnon, Cynthia; Laberge, Luc; Tremblay, Carmen; Côté, Charlotte; Leclerc, Nadine; Mathieu, Jean

    2009-01-01

    Neuromuscular hereditary disorders require long-term multidisciplinary rehabilitation management. Although the need for coordinated healthcare management has long been recognized, most neuromuscular disorders are still lacking clinical guidelines about their long-term management and structured evaluation plan with associated services. One of the most prevalent adult-onset neuromuscular disorders, myotonic dystrophy type 1, generally presents several comorbidities and a variable clinical picture, making management a constant challenge. This article presents a healthcare follow-up plan and proposes a nursing case management within a disease management program as an innovative and promising approach. This disease management program and model consists of eight components including population identification processes, evidence-based practice guidelines, collaborative practice, patient self-management education, and process outcomes evaluation (Disease Management Association of America, 2004). It is believed to have the potential to significantly improve healthcare management for neuromuscular hereditary disorders and will prove useful to nurses delivering and organizing services for this population.

  18. Preparing for Emergencies: A Checklist for People with Neuromuscular Diseases

    MedlinePlus

    TORNADO • FLASH FLOOD • EARTHQUAKE • WINTER STORM • HURRICANE • FIRE • HAZARDOUS MATERIALS SPILL Preparing for Emergencies A Checklist for People with Neuromuscular Diseases F or the millions of Americans with limited ...

  19. The role of proprioception and neuromuscular stability in carpal instabilities.

    PubMed

    Hagert, E; Lluch, A; Rein, S

    2016-01-01

    Carpal stability has traditionally been defined as dependent on the articular congruity of joint surfaces, the static stability maintained by intact ligaments, and the dynamic stability caused by muscle contractions resulting in a compression of joint surfaces. In the past decade, a fourth factor in carpal stability has been proposed, involving the neuromuscular and proprioceptive control of joints. The proprioception of the wrist originates from afferent signals elicited by sensory end organs (mechanoreceptors) in ligaments and joint capsules that elicit spinal reflexes for immediate joint stability, as well as higher order neuromuscular influx to the cerebellum and sensorimotor cortices for planning and executing joint control. The aim of this review is to provide an understanding of the role of proprioception and neuromuscular control in carpal instabilities by delineating the sensory innervation and the neuromuscular control of the carpus, as well as descriptions of clinical applications of proprioception in carpal instabilities. PMID:26115684

  20. Muscle ultrasound quantifies segmental neuromuscular outcome in pediatric myelomeningocele.

    PubMed

    Verbeek, Renate J; Hoving, Eelco W; Maurits, Natalia M; Brouwer, Oebele F; van der Hoeven, Johannes H; Sival, Deborah A

    2014-01-01

    In pediatric spina bifida aperta (SBA), non-invasive assessment of neuromuscular integrity by muscle ultrasound density (MUD) could provide important information about the clinical condition. We therefore aimed to determine the association between pediatric SBA MUD and segmental neurologic function. We included 23 children (age range: 1-18 y) with SBA with L4-5 lesions, and we associated SBA MUD with control values and segmental neuromuscular function. Results revealed that MUD outcomes in the lower extremities: (i) are independent of age, (ii) exceed control values, (iii) differ intra-individually (i.e., between the left and right sides in the same individual) in association with segmental neuromuscular function. We concluded that SBA leg MUD can quantify the segmental neuromuscular condition throughout childhood.

  1. CLASP2-dependent microtubule capture at the neuromuscular junction membrane requires LL5β and actin for focal delivery of acetylcholine receptor vesicles

    PubMed Central

    Basu, Sreya; Sladecek, Stefan; Martinez de la Peña y Valenzuela, Isabel; Akaaboune, Mohammed; Smal, Ihor; Martin, Katrin; Galjart, Niels; Brenner, Hans Rudolf

    2015-01-01

    A hallmark of the neuromuscular junction (NMJ) is the high density of acetylcholine receptors (AChRs) in the postsynaptic muscle membrane. The postsynaptic apparatus of the NMJ is organized by agrin secreted from motor neurons. The mechanisms that underlie the focal delivery of AChRs to the adult NMJ are not yet understood in detail. We previously showed that microtubule (MT) capture by the plus end–tracking protein CLASP2 regulates AChR density at agrin-induced AChR clusters in cultured myotubes via PI3 kinase acting through GSK3β. Here we show that knockdown of the CLASP2-interaction partner LL5β by RNAi and forced expression of a CLASP2 fragment blocking the CLASP2/LL5β interaction inhibit microtubule capture. The same treatments impair focal vesicle delivery to the clusters. Consistent with these findings, knockdown of LL5β at the NMJ in vivo reduces the density and insertion of AChRs into the postsynaptic membrane. MT capture and focal vesicle delivery to agrin-induced AChR clusters are also inhibited by microtubule- and actin-depolymerizing drugs, invoking both cytoskeletal systems in MT capture and in the fusion of AChR vesicles with the cluster membrane. Combined our data identify a transport system, organized by agrin through PI3 kinase, GSK3β, CLASP2, and LL5β, for precise delivery of AChR vesicles from the subsynaptic nuclei to the overlying synaptic membrane. PMID:25589673

  2. RecO acts with RecF and RecR to protect and maintain replication forks blocked by UV-induced DNA damage in Escherichia coli.

    PubMed

    Chow, Kin-Hoe; Courcelle, Justin

    2004-01-30

    In Escherichia coli, recF and recR are required to stabilize and maintain replication forks arrested by UV-induced DNA damage. In the absence of RecF, replication fails to recover, and the nascent lagging strand of the arrested replication fork is extensively degraded by the RecQ helicase and RecJ nuclease. recO mutants are epistatic with recF and recR with respect to recombination and survival assays after DNA damage. In this study, we show that RecO functions with RecF and RecR to protect the nascent lagging strand of arrested replication forks after UV-irradiation. In the absence of RecO, the nascent DNA at arrested replication forks is extensively degraded and replication fails to recover. The extent of nascent DNA degradation is equivalent in single, double, or triple mutants of recF, recO, or recR, and the degradation is dependent upon RecJ and RecQ functions. Because RecF has been shown to protect the nascent lagging strand from degradation, these observations indicate that RecR and RecO function with RecF to protect the same nascent strand of the arrested replication fork and are likely to act at a common point during the recovery process. We discuss these results in relation to the biochemical and cellular properties of RecF, RecO, and RecR and their potential role in loading RecA filaments to maintain the replication fork structure after the arrest of replication by UV-induced DNA damage. PMID:14625283

  3. For the inactivation of mold spores by UVC irradiation, with ozone acting as a promoter, TiO2 nanoparticles may act better as a "sun block" than as a photocatalytic disinfectant.

    PubMed

    Gong, Jia-You; Chen, Yen-Chi; Huang, Yi-Ting; Tsai, Ming-Chien; Yu, Kuo-Pin

    2014-09-01

    Fungal spores are known as critical indoor allergens, and indoor air purification techniques including photocatalytic disinfection using titanium dioxide (TiO2), ultraviolet germicidal irradiation (UVGI) and ozonation, have been considerably investigated. However, most of the research is in regard to photocatalytic disinfection, focused on the anti-bacterial efficacy of TiO2 nanoparticles (NPs). Furthermore, some research even showed that the photocatalytic antifungal efficacy of TiO2 NPs may not be that significant. Thus, investigating the reasons behind the non-significant antifungal efficacy of TiO2 photocatalytic disinfection and enhancing the antifungal efficacy is indispensable. In this study, ozone was employed to improve the photocatalytic antifungal efficacy of the TiO2 NPs and nano-metal supported on TiO2 NPs. The commercial TiO2 NPs (Degussa (Evonik) P25) served as a good support, and incipient wetness impregnation was successfully exploited to prepare oxidized nano-metals (Ag, Cu and Ni) in this study. There were two surfaces (quartz and putty) used in the inactivation experiments of Aspergillus niger spores which were manipulated under two conditions: exposed to ultraviolet (UVC) light , and exposed to UVC and ozone simultaneously. The SEM images demonstrated that the spores were sheltered from UVC light in the microcracks between TiO2 agglomerates. When irradiating with UVC, the A. niger spores on the two testing surfaces, without TiO2 NPs, were inactivated faster than those with TiO2 NPs, implying a "sun block" effect of this material and a lower photocatalytic antifungal efficacy than UVGI. On both surfaces, the inactivation rate constants (k) of A. niger spores exposed to UVC and ozone simultaneously (on quartz: k = 2.09-6.94 h(-1), on putty: k = 3.17-6.66 h(-1)) were better than those exposed to only UVC (on quartz: k = 1.80-5.89 h(-1); on putty: k = 2.97-3.98 h(-1)), indicating ozone can enhance the UVGI antifungal efficacy. PMID:25007943

  4. Neuromuscular Fatigue During 200 M Breaststroke

    PubMed Central

    Conceição, Ana; Silva, António J.; Barbosa, Tiago; Karsai, István; Louro, Hugo

    2014-01-01

    The aims of this study were: i) to analyze activation patterns of four upper limb muscles (duration of the active and non-active phase) in each lap of 200m breaststroke, ii) quantify neuromuscular fatigue, with kinematics and physiologic assessment. Surface electromyogram was collected for the biceps brachii, deltoid anterior, pectoralis major and triceps brachii of nine male swimmers performing a maximal 200m breaststroke trial. Swimming speed, SL, SR, SI decreased from the 1st to the 3rd lap. SR increased on the 4th lap (35.91 ± 2.99 stroke·min-1). Peak blood lactate was 13.02 ± 1.72 mmol·l-1 three minutes after the maximal trial. The EMG average rectified value (ARV) increased at the end of the race for all selected muscles, but the deltoid anterior and pectoralis major in the 1st lap and for biceps brachii, deltoid anterior and triceps brachii in the 4th lap. The mean frequency of the power spectral density (MNF) decreased at the 4th lap for all muscles. These findings suggest the occurrence of fatigue at the beginning of the 2nd lap in the 200m breaststroke trial, characterized by changes in kinematic parameters and selective changes in upper limb muscle action. There was a trend towards a non-linear fatigue state. Key Points Fatigue in the upper limbs occurs in different way as it described by 100m swimming events. Neuromuscular fatigue was estimated by analyzing the physiological changes (high blood lactate concentrations), biomechanical changes in the swimming stroke characteristics (decreased in swimming velocity), and by the changes in the EMG amplitude and frequency parameters at the end of the swimming bout. The amplitude signal of EMG provided by the ARV demonstrated an increase at the end with the respect to the beginning for all muscles under study, excepted for the muscle deltoid anterior. The mean frequency (MNF) in our study decrease at the end of the swimming in the 4th lap relative to the 1st lap for all muscles under observation, along the

  5. Animal models for genetic neuromuscular diseases.

    PubMed

    Vainzof, Mariz; Ayub-Guerrieri, Danielle; Onofre, Paula C G; Martins, Poliana C M; Lopes, Vanessa F; Zilberztajn, Dinorah; Maia, Lucas S; Sell, Karen; Yamamoto, Lydia U

    2008-03-01

    The neuromuscular disorders are a heterogeneous group of genetic diseases, caused by mutations in genes coding sarcolemmal, sarcomeric, and citosolic muscle proteins. Deficiencies or loss of function of these proteins leads to variable degree of progressive loss of motor ability. Several animal models, manifesting phenotypes observed in neuromuscular diseases, have been identified in nature or generated in laboratory. These models generally present physiological alterations observed in human patients and can be used as important tools for genetic, clinic, and histopathological studies. The mdx mouse is the most widely used animal model for Duchenne muscular dystrophy (DMD). Although it is a good genetic and biochemical model, presenting total deficiency of the protein dystrophin in the muscle, this mouse is not useful for clinical trials because of its very mild phenotype. The canine golden retriever MD model represents a more clinically similar model of DMD due to its larger size and significant muscle weakness. Autosomal recessive limb-girdle MD forms models include the SJL/J mice, which develop a spontaneous myopathy resulting from a mutation in the Dysferlin gene, being a model for LGMD2B. For the human sarcoglycanopahties (SG), the BIO14.6 hamster is the spontaneous animal model for delta-SG deficiency, whereas some canine models with deficiency of SG proteins have also been identified. More recently, using the homologous recombination technique in embryonic stem cell, several mouse models have been developed with null mutations in each one of the four SG genes. All sarcoglycan-null animals display a progressive muscular dystrophy of variable severity and share the property of a significant secondary reduction in the expression of the other members of the sarcoglycan subcomplex and other components of the Dystrophin-glycoprotein complex. Mouse models for congenital MD include the dy/dy (dystrophia-muscularis) mouse and the allelic mutant dy(2J)/dy(2J) mouse

  6. Neuromuscular dentistry: Occlusal diseases and posture

    PubMed Central

    Khan, Mohd Toseef; Verma, Sanjeev Kumar; Maheshwari, Sandhya; Zahid, Syed Naved; Chaudhary, Prabhat K.

    2013-01-01

    Neuromuscular dentistry has been a controversial topic in the field of dentistry and still remains debatable. The issue of good occlusion and sound health has been repeatedly discussed. Sometimes we get complains of sensitive teeth and sometimes of tired facial muscles on getting up in the morning. Owing to the intimate relation of masticatory apparatus with the cranium and cervico-scapular muscular system, the disorders in any system, draw attention from concerned clinicians involved in management, to develop an integrated treatment protocol for the suffering patients. There may be patients reporting to the dental clinics after an occlusal restoration or extraction, having pain in or around the temporomandibular joint, headache or neck pain. Although their esthetic demands must not be undermined during the course of treatment plan, whenever dental treatment of any sort is planned, occlusion/bite should be given prime importance. Very few dentist are able to diagnose the occlusal disease and of those who diagnose many people resort to aggressive treatment modalities. This paper aims to report the signs of occlusal disease, and discuss their association with TMDs and posture. PMID:25737904

  7. Neuromuscular performance characteristics in elite female athletes.

    PubMed

    Huston, L J; Wojtys, E M

    1996-01-01

    The purpose of this research was to identify possible predisposing neuromuscular factors for knee injuries, particularly anterior cruciate ligament tears in female athletes by investigating anterior knee laxity, lower extremity muscle strength, endurance, muscle reaction time, and muscle recruitment order in response to anterior tibial translation. We recruited four subject groups: elite female (N = 40) and male (N = 60) athletes and sex-matched nonathletic controls (N = 40). All participants underwent a subjective evaluation of knee function, arthrometer measurement of anterior tibial translation, isokinetic dynamometer strength and endurance tests at 60 and 240 deg/sec, and anterior tibial translation stress tests. Dynamic stress testing of muscles demonstrated less anterior tibial translation in the knees of the athletes (both men and women) compared with the nonathletic controls. Female athletes and controls demonstrated more anterior tibial laxity than their male counterparts and significantly less muscle strength and endurance. Compared with the male athletes, the female athletes took significantly longer to generate maximum hamstring muscle torque during isokinetic testing. Although no significant differences were found in either spinal or cortical muscle reaction times, the muscle recruitment order in some female athletes was markedly different. The female athletes appeared to rely more on their quadriceps muscles in response to anterior tibial translation; the three other test groups relied more on their hamstring muscles for initial knee stabilization.

  8. The neuromuscular differential diagnosis of joint hypermobility.

    PubMed

    Donkervoort, S; Bonnemann, C G; Loeys, B; Jungbluth, H; Voermans, N C

    2015-03-01

    Joint hypermobility is the defining feature of various inherited connective tissue disorders such as Marfan syndrome and various types of Ehlers-Danlos syndrome and these will generally be the first conditions to be considered by geneticists and pediatricians in the differential diagnosis of a patient presenting with such findings. However, several congenital and adult-onset inherited myopathies also present with joint hypermobility in the context of often only mild-to-moderate muscle weakness and should, therefore, be included in the differential diagnosis of joint hypermobility. In fact, on the molecular level disorders within both groups represent different ends of the same spectrum of inherited extracellular matrix (ECM) disorders. In this review we will summarize the measures of joint hypermobility, illustrate molecular mechanisms these groups of disorders have in common, and subsequently discuss the clinical features of: 1) the most common connective tissue disorders with myopathic or other neuromuscular features: Ehlers-Danlos syndrome, Marfan syndrome and Loeys-Dietz syndrome; 2) myopathy and connective tissue overlap disorders (muscle extracellular matrix (ECM) disorders), including collagen VI related dystrophies and FKBP14 related kyphoscoliotic type of Ehlers-Danlos syndrome; and 3) various (congenital) myopathies with prominent joint hypermobility including RYR1- and SEPN1-related myopathy. The aim of this review is to assist clinical geneticists and other clinicians with recognition of these disorders. PMID:25821091

  9. Pathophysiological actions of neuropathy-related anti-ganglioside antibodies at the neuromuscular junction

    PubMed Central

    Plomp, Jaap J; Willison, Hugh J

    2009-01-01

    The outer leaflet of neuronal membranes is highly enriched in gangliosides. Therefore, specific neuronal roles have been attributed to this family of sialylated glycosphingolipids, e.g. in modulation of ion channels and transporters, neuronal interaction and recognition, temperature adaptation, Ca2+ homeostasis, axonal growth, (para)node of Ranvier stability and synaptic transmission. Recent developmental, ageing and injury studies on transgenic mice lacking subsets of gangliosides indicate that gangliosides are involved in maintenance rather than development of the nervous system and that ganglioside family members are able to act in a mutually compensatory manner. Besides having physiological functions, gangliosides are the likely antigenic targets of autoantibodies present in Guillain-Barré syndrome (GBS), a group of neuropathies with clinical symptoms of motor- and/or sensory peripheral nerve dysfunction. Antibody binding to peripheral nerves is thought to either interfere with ganglioside function or activate complement, causing axonal damage and thereby disturbed action potential conduction. The presynaptic motor nerve terminal at the neuromuscular junction (NMJ) may be a prominent target because it is highly enriched in gangliosides and lies outside the blood–nerve barrier, allowing antibody access. The ensuing neuromuscular synaptopathy might contribute to the muscle weakness in GBS patients. Several groups, including our own, have studied the effects of anti-ganglioside antibodies in ex vivo and in vivo experimental settings at mouse NMJs. Here, after providing a background overview on ganglioside synthesis, localization and physiology, we will review those studies, which clearly show that anti-ganglioside antibodies are capable of binding to NMJs and thereby can exert a variety of pathophysiological effects. Furthermore, we will discuss the human clinical electrophysiological and histological evidence produced so far of the existence of a neuromuscular

  10. Lumbopelvic flexibility modulates neuromuscular responses during trunk flexion-extension.

    PubMed

    Sánchez-Zuriaga, Daniel; Artacho-Pérez, Carla; Biviá-Roig, Gemma

    2016-06-01

    Various stimuli such as the flexibility of lumbopelvic structures influence the neuromuscular responses of the trunk musculature, leading to different load sharing strategies and reflex muscle responses from the afferents of lumbopelvic mechanoreceptors. This link between flexibility and neuromuscular response has been poorly studied. The aim of this study was to investigate the relationship between lumbopelvic flexibility and neuromuscular responses of the erector spinae, hamstring and abdominal muscles during trunk flexion-extension. Lumbopelvic movement patterns were measured in 29 healthy women, who were separated into two groups according to their flexibility during trunk flexion-extension. The electromyographic responses of erector spinae, rectus abdominis and biceps femoris were also recorded. Subjects with greater lumbar flexibility had significantly less pelvic flexibility and vice versa. Subjects with greater pelvic flexibility had a higher rate of relaxation and lower levels of hamstring activation during maximal trunk flexion. The neuromuscular response patterns of the hamstrings seem partially modulated by pelvic flexibility. Not so with the lumbar erector spinae and lumbar flexibility, despite the assertions of some previous studies. The results of this study improve our knowledge of the relationships between trunk joint flexibility and neuromuscular responses, a relationship which may play a role in low back pain. PMID:27155332

  11. Lumbopelvic flexibility modulates neuromuscular responses during trunk flexion-extension.

    PubMed

    Sánchez-Zuriaga, Daniel; Artacho-Pérez, Carla; Biviá-Roig, Gemma

    2016-06-01

    Various stimuli such as the flexibility of lumbopelvic structures influence the neuromuscular responses of the trunk musculature, leading to different load sharing strategies and reflex muscle responses from the afferents of lumbopelvic mechanoreceptors. This link between flexibility and neuromuscular response has been poorly studied. The aim of this study was to investigate the relationship between lumbopelvic flexibility and neuromuscular responses of the erector spinae, hamstring and abdominal muscles during trunk flexion-extension. Lumbopelvic movement patterns were measured in 29 healthy women, who were separated into two groups according to their flexibility during trunk flexion-extension. The electromyographic responses of erector spinae, rectus abdominis and biceps femoris were also recorded. Subjects with greater lumbar flexibility had significantly less pelvic flexibility and vice versa. Subjects with greater pelvic flexibility had a higher rate of relaxation and lower levels of hamstring activation during maximal trunk flexion. The neuromuscular response patterns of the hamstrings seem partially modulated by pelvic flexibility. Not so with the lumbar erector spinae and lumbar flexibility, despite the assertions of some previous studies. The results of this study improve our knowledge of the relationships between trunk joint flexibility and neuromuscular responses, a relationship which may play a role in low back pain.

  12. Presynaptic snake beta-neurotoxins produce tetanic fade and endplate potential run-down during neuromuscular blockade in mouse diaphragm.

    PubMed

    Wilson, H I; Nicholson, G M

    1997-11-01

    The present study investigated the ability of a number of presynaptic snake neurotoxins (snake beta-neurotoxins) to produce nerve-evoked train-of-four fade, tetanic fade and endplate potential run-down during the development of neuromuscular blockade in the isolated mouse phrenic-hemidiaphragm nerve-muscle preparation. All the snake beta-neurotoxins tested, with the exception of notexin, produced train-of-four and tetanic fade of nerve-evoked isometric muscle contractions. Train-of-four fade was not present during the initial depressant or facilitatory phases of muscle tension produced by the snake beta-neurotoxins but developed progressively during the final depressant phase that precedes complete neuromuscular blockade. The 'non-neurotoxic' bovine pancreatic phospholipase A2 and the 'low-toxicity' phospholipase A2 from Naja naja atra venom failed to elicit train-of-four fade, indicating that the phospholipase activity of the snake beta-neurotoxins is not responsible for the development of fade. Intracellular recording of endplate potentials (EPPs) elicited by nerve-evoked trains of stimuli showed a progressive run-down in EPP amplitude during the train following incubation with all snake beta-neurotoxins except notexin. Again this run-down in EPP amplitude was confined to the final depressant phase of snake beta-neurotoxin action. However when EPP amplitude fell to near uniquantal levels (< 3 mV) the extent of toxin induced-fade was reduced. Unlike postjunctional snake alpha-neurotoxins, prejunctional snake beta-neurotoxins interfere with acetylcholine release at the neuromuscular junction during the development of neuromuscular blockade. This study provides further support for the hypothesis that fade in twitch and tetanic muscle tension is due to an underlying rundown in EPP amplitude resulting from a prejunctional alteration of transmitter release rather than a use-dependent block of postjunctional nicotinic receptors.

  13. Pain in Youths With Neuromuscular Disease

    PubMed Central

    Engel, Joyce M.; Kartin, Deborah; Carter, Gregory T.; Jensen, Mark P.; Jaffe, Kenneth M.

    2011-01-01

    To examine the prevalence and characteristics of pain in children with neuromuscular disease (NMD), 42 youths with NMD underwent a comprehensive evaluation including a detailed intake interview and structured questionnaire that included demographic and functional data. Youths who reported chronic pain were further queried about pain characteristics, locations, and intensity using an 11-point numerical rating scale and a modified Brief Pain Inventory (BPI). The sample consisted of 24 males (57%) and 18 females (43%), ages ranging from 9 to 20 years (M = 14.8, SD = 2.96). Participants included 14 (37%) with Duchenne-muscular dystrophy, 6 (14%) with myotonic dystrophy, 2 (5%) with Becker dystrophy, 2 (5%) with limb-girdle dystrophy, 2 (5%) with congenital muscular dystrophy, 1 (2%) facioscapulohumeral, and 15 (36%) were classified as “other NMD.” Twenty-one (50%) were ambulatory; 26 (62%) used power wheelchairs/scooters, 9 (2%) used manual wheelchairs, 3 (.07%) used crutches/canes, and 1 (2%) used a walker. A total of 23 (55%) of the youths reported having chronic pain. Current pain intensity was 1.30(range=0–6), mean pain intensity over the past week was 2.39 (range = 0–7), mean pain duration was 8.75 hours (SD=12.84). Pain in the legs was most commonly reported and 83% reported using pain medications. This study indicates that chronic pain is a significant problem in youths with NMD. These data strongly support making comprehensive pain assessment and management an integral part of the standard of care for youths with NMD. PMID:19820205

  14. Neuromuscular junction channelopathies: a brief overview.

    PubMed

    Newsom-Davis, John

    2005-12-01

    The neuromuscular junction lacks the protection of the blood-nerve barrier and is vulnerable to antibody-mediated disorders. In myasthenia gravis (MG), 85% of patients have IgG antibodies to acetylcholine receptors (AChRs). About half the remaining patients have IgG antibodies to Muscle Specific Kinase (MuSK), an AChR-associated transmembrane post-synaptic protein concerned in AChR aggregation. Bulbar weakness is typically predominant in this form of MG, and females are more often affected. The Lambert-Eaton Myasthenic Syndrome (LEMS) can occur in a paraneoplastic form (P-LEMS) usually with small cell lung cancer, or in a non-paraneoplastic form (NP-LEMS). In both, IgG antibodies to nerve terminal voltage-gated calcium channels (VGCCs), detectable in over 90% of patients, lead to VGCC loss and impaired quantal release of transmitter and may be implicated in the occasionally associated cerebellar ataxia. Neuromyotonia (NMT) and Cramp-Fasciculation syndrome (C-FS) are manifestations of peripheral nerve hyperexcitability and share some clinical and electromyographic features. Antibodies to voltage-gated potassium channels (VGKCs) are present in about 40% of NMT patients, but less frequently in C-FS, and appear to cause loss of functional VGKCs. They may also be implicated in the Maladie de Morvan and limbic encephalitis that can associate with NMT: The antibodies described here provide valuable aids to diagnosis and management. The Congenital Myasthenic Syndromes are a group of genetically determined heterogeneous disorders, usually recessively inherited. The commonest mutation sites appear to be the acetylcholine receptor epsilon-subunit and rapsyn.

  15. Block People.

    ERIC Educational Resources Information Center

    Peterson, Rayma

    1999-01-01

    Discusses an activity in which students in an after-school art class drew one another on pieces of 2-by-4 scrap lumber in order to create a class portrait in three dimensions. Stresses that the portraits on the wood blocks were done in-the-round, or each side was covered. (CMK)

  16. Single Fiber Electromyographic Jitter to Detect Acute Changes in Neuromuscular Function in Young and Adult Rats

    EPA Science Inventory

    Introduction: Exposure to irreversible cholinesterase (ChE)-inhibiting compounds, such as organophosphates may produce neuromuscular dysfunction. However, less is known about changes in neuromuscular transmission after treatment with reversible ChE-inhibitors. These studies adapt...

  17. Genetic and evolutionary analysis of the Drosophila larval neuromuscular junction

    NASA Astrophysics Data System (ADS)

    Campbell, Megan

    Although evolution of brains and behaviors is of fundamental biological importance, we lack comprehensive understanding of the general principles governing these processes or the specific mechanisms and molecules through which the evolutionary changes are effected. Because synapses are the basic structural and functional units of nervous systems, one way to address these problems is to dissect the genetic and molecular pathways responsible for morphological evolution of a defined synapse. I have undertaken such an analysis by examining morphology of the larval neuromuscular junction (NMJ) in wild caught D. melanogaster as well as in over 20 other species of Drosophila. Whereas variation in NMJ morphology within a species is limited, I discovered a surprisingly extensive variation among different species. Compared with evolution of other morphological traits, NMJ morphology appears to be evolving very rapidly. Moreover, my data indicate that natural selection rather than genetic drift is primarily responsible for evolution of NMJ morphology. To dissect underlying molecular mechanisms that may govern NMJ growth and evolutionary divergence, I focused on a naturally occurring variant in D. melanogaster that causes NMJ overgrowth. I discovered that the variant mapped to Mob2, a gene encoding a kinase adapter protein originally described in yeast as a member of the Mitotic Exit Network (MEN). I have subsequently examined mutations in the Drosophila orthologs of all the core components of the yeast MEN and found that all of them function as part of a common pathway that acts presynaptically to negatively regulate NMJ growth. As in the regulation of yeast cytokinesis, these components of the MEN appear to act ultimately by regulating actin dynamics during the process of bouton growth and division. These studies have thus led to the discovery of an entirely new role for the MEN---regulation of synaptic growth---that is separate from its function in cell division. This work

  18. Postsynaptic actin regulates active zone spacing and glutamate receptor apposition at the Drosophila neuromuscular junction.

    PubMed

    Blunk, Aline D; Akbergenova, Yulia; Cho, Richard W; Lee, Jihye; Walldorf, Uwe; Xu, Ke; Zhong, Guisheng; Zhuang, Xiaowei; Littleton, J Troy

    2014-07-01

    Synaptic communication requires precise alignment of presynaptic active zones with postsynaptic receptors to enable rapid and efficient neurotransmitter release. How transsynaptic signaling between connected partners organizes this synaptic apparatus is poorly understood. To further define the mechanisms that mediate synapse assembly, we carried out a chemical mutagenesis screen in Drosophila to identify mutants defective in the alignment of active zones with postsynaptic glutamate receptor fields at the larval neuromuscular junction. From this screen we identified a mutation in Actin 57B that disrupted synaptic morphology and presynaptic active zone organization. Actin 57B, one of six actin genes in Drosophila, is expressed within the postsynaptic bodywall musculature. The isolated allele, act(E84K), harbors a point mutation in a highly conserved glutamate residue in subdomain 1 that binds members of the Calponin Homology protein family, including spectrin. Homozygous act(E84K) mutants show impaired alignment and spacing of presynaptic active zones, as well as defects in apposition of active zones to postsynaptic glutamate receptor fields. act(E84K) mutants have disrupted postsynaptic actin networks surrounding presynaptic boutons, with the formation of aberrant actin swirls previously observed following disruption of postsynaptic spectrin. Consistent with a disruption of the postsynaptic actin cytoskeleton, spectrin, adducin and the PSD-95 homolog Discs-Large are all mislocalized in act(E84K) mutants. Genetic interactions between act(E84K) and neurexin mutants suggest that the postsynaptic actin cytoskeleton may function together with the Neurexin-Neuroligin transsynaptic signaling complex to mediate normal synapse development and presynaptic active zone organization.

  19. Neuromuscular hip biomechanics and pathology in the athlete.

    PubMed

    Torry, Michael R; Schenker, Mara L; Martin, Hal D; Hogoboom, Doug; Philippon, Marc J

    2006-04-01

    Although hip arthroscopic techniques have been developed and evolved over the last 5 to 10 years to help active athletes, the mechanisms of athletic hip injuries across various sports are not well understood. The purpose of this article is to review the literature related to the osseous and ligamentous support as well as the neuromuscular control strategies associated with hip joint mechanics. The neuromuscular contributions to hip stability and mobility with respect to gait will be provided because this data represents the largest body of knowledge regarding hip function. Further, this article will present and describe probable mechanisms of injury in sporting activities most often associated with hip injury in the young athlete.

  20. Snake and Spider Toxins Induce a Rapid Recovery of Function of Botulinum Neurotoxin Paralysed Neuromuscular Junction

    PubMed Central

    Duregotti, Elisa; Zanetti, Giulia; Scorzeto, Michele; Megighian, Aram; Montecucco, Cesare; Pirazzini, Marco; Rigoni, Michela

    2015-01-01

    Botulinum neurotoxins (BoNTs) and some animal neurotoxins (β-Bungarotoxin, β-Btx, from elapid snakes and α-Latrotoxin, α-Ltx, from black widow spiders) are pre-synaptic neurotoxins that paralyse motor axon terminals with similar clinical outcomes in patients. However, their mechanism of action is different, leading to a largely-different duration of neuromuscular junction (NMJ) blockade. BoNTs induce a long-lasting paralysis without nerve terminal degeneration acting via proteolytic cleavage of SNARE proteins, whereas animal neurotoxins cause an acute and complete degeneration of motor axon terminals, followed by a rapid recovery. In this study, the injection of animal neurotoxins in mice muscles previously paralyzed by BoNT/A or /B accelerates the recovery of neurotransmission, as assessed by electrophysiology and morphological analysis. This result provides a proof of principle that, by causing the complete degeneration, reabsorption, and regeneration of a paralysed nerve terminal, one could favour the recovery of function of a biochemically- or genetically-altered motor axon terminal. These observations might be relevant to dying-back neuropathies, where pathological changes first occur at the neuromuscular junction and then progress proximally toward the cell body. PMID:26670253

  1. Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane

    PubMed Central

    Schmidt, Nadine; Basu, Sreya; Sladecek, Stefan; Gatti, Sabrina; van Haren, Jeffrey; Treves, Susan; Pielage, Jan

    2012-01-01

    Agrin is the major factor mediating the neuronal regulation of postsynaptic structures at the vertebrate neuromuscular junction, but the details of how it orchestrates this unique three-dimensional structure remain unknown. Here, we show that agrin induces the formation of the dense network of microtubules in the subsynaptic cytoplasm and that this, in turn, regulates acetylcholine receptor insertion into the postsynaptic membrane. Agrin acted in part by locally activating phosphatidylinositol 3-kinase and inactivating GSK3β, which led to the local capturing of dynamic microtubules at agrin-induced acetylcholine receptor (AChR) clusters, mediated to a large extent by the microtubule plus-end tracking proteins CLASP2 and CLIP-170. Indeed, in the absence of CLASP2, microtubule plus ends at the subsynaptic muscle membrane, the density of synaptic AChRs, the size of AChR clusters, and the numbers of subsynaptic muscle nuclei with their selective gene expression programs were all reduced. Thus, the cascade linking agrin to CLASP2-mediated microtubule capturing at the synaptic membrane is essential for the maintenance of a normal neuromuscular phenotype. PMID:22851317

  2. Relationships between block-of-twitch and train-of-four fade in the mouse phrenic nerve-diaphragm preparation.

    PubMed

    Storella, R J; Slomowitz, S A; Rosenberg, H

    1991-04-01

    The relationships between the block-of-twitch and train-of-four fade in the presence of nondepolarizing neuromuscular blocking drugs (d-tubocurarine, vecuronium and pancuronium) were examined in vitro by measuring the contractile tension from mouse phrenic nerve-diaphragm preparations. The slope of the block/fade relationship differed between onset of and recovery from neuromuscular block following single doses of d-tubocurarine, vecuronium or pancuronium. Decreasing the dose of d-tubocurarine or using a divided dose technique to accelerate onset (i.e., priming) increased the amount of fade for a given amount of block. In addition, the block/fade relationships for cumulative dosing and sequential dilution were the same when measurements were made at steady-state for several doses. It is concluded that the block/fade relationship in the mouse phrenic nerve-diaphragm preparation is variable, and is related to the time course of the neuromuscular block. In addition, the block/fade relationships for d-tubocurarine, vecuronium and pancuronium did not differ when determined at steady-state.

  3. Inspiratory muscle training in the patient with neuromuscular disease.

    PubMed

    McCool, F D; Tzelepis, G E

    1995-11-01

    Pulmonary complications due to respiratory muscle dysfunction are commonly a source of morbidity and mortality in patients with neuromuscular diseases. This review discusses the adverse effects of respiratory muscle weakness on pulmonary mechanics and examines the role that inspiratory muscle training may play in reversing pulmonary dysfunction in these individuals. In asymptomatic persons, it is well established that the inspiratory muscles can be trained to increase both force and endurance. In patients with neuromuscular diseases, the effects of training protocols on force and endurance are more controversial. This article reviews seven studies that have evaluated respiratory muscle training in a total of 75 patients with varied neuromuscular disorders. Training regimens included breathing through inspiratory resistive loads and isocapnic hyperpnea. Despite methodologic differences among studies, investigators have generally shown that the inspiratory muscles are similar to other skeletal muscle groups in that they can be trained for both force and endurance in these patients. The training-related improvements in inspiratory muscle performance are more pronounced in patients who are less severely affected by their disease. In those patients who have disease to the extent that they are already retaining carbon dioxide, there is little change in force or endurance with training. In these individuals, the inspiratory muscles may already be working at a level sufficiently severe to provide a training stimulus with each breath. No adverse effects of inspiratory muscle training were reported. Inspiratory muscle training can improve force and endurance in patients with neuromuscular weakness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7480122

  4. Neuromuscular junction integrity after chronic nerve compression injury.

    PubMed

    Mozaffar, Tahseen; Strandberg, Erika; Abe, Kazuko; Hilgenberg, Lutz G; Smith, Martin A; Gupta, Ranjan

    2009-01-01

    Chronic nerve compression injuries (CNC) are progressive demyelinating disorders characterized by a gradual decline of the nerve conduction velocity (NCV) in the affected nerve region. CNC injury induces a robust Schwann cell response with axonal sprouting, but without morphologic evidence of axonal injury. We hypothesize that early CNC injury occurs without damage to neuromuscular junction of motor axons. A well-established animal model was used to assess for damage to motor axons. As sprouting is considered a hallmark of regeneration during and after axonal degeneration and sprouting was confirmed visually at 2 weeks in CNC animals, we assessed for axonal degeneration in motor nerves after CNC by evaluating the integrity of the neuromuscular junction. NCV exhibited a gradual progressive decline consistent with the human condition. Compound motor action potential amplitudes decreased slightly immediately and plateaued, indicating that there was not sustained and increasing axonal loss. Sprouting was confirmed using immunofluorescence and by an increase in number of unmyelinated axons and Remak bundles. Blind analysis of the neuromuscular junction showed no difference between control and CNC images, indicating that there was no evidence for end-unit axonal loss in the soleus muscle. Because the progressive decline in NCV was not paired with a similar progressive decline in amplitude, it is likely that axonal loss is not responsible for slowing of action potentials. Blind analysis of the neuromuscular junction provides further evidence that the axonal sprouting seen early after CNC injury is not a consequence of axonal degeneration in the motor nerves. PMID:18655131

  5. Mainstreaming Children with a Neuromuscular Disease: A Map of Concerns.

    ERIC Educational Resources Information Center

    Strong, Kristine; Sandoval, Jonathan

    1999-01-01

    Four focus groups (n=21) were conducted to gather information about coping issues and teacher attitudes related to the education of children with a neuromuscular disease. Results indicate a need for better home/school communication, a need to establish children's sense of competence, and a need for improved peer relationships. (Author/CR)

  6. Drug Development and Challenges for Neuromuscular Clinical Trials.

    PubMed

    El Mouelhi, Mohamed

    2016-03-01

    Drug development process faces many challenges, including those encountered in clinical trials for neuromuscular diseases. Drug development is a lengthy and highly costly process. Out of 10 compounds entering first study in man (phase 1), only one compound reaches the market after an average of 14 years with a cost of $2.7 billion. Nevertheless, according to the Centers for Medicare and Medicaid services, prescription drugs constituted only 9 % of each health care dollar spent in USA in 2013. Examples of challenges encountered in neuromuscular clinical trials include lack of validated patient-reported outcome tools, blinding issues, and the use of placebo in addition to lack of health authority guidance for orphan diseases. Patient enrollment challenge is the leading cause of missed clinical trial deadlines observed in about 80 % of clinical trials, resulting in delayed availability of potentially life-saving therapies. Another specific challenge introduced by recent technology is the use of social media and risk of bias. Sharing personal experiences while in the study could easily introduce bias among patients that would interfere with accurate interpretation of collected data. To minimize this risk, recent neuromuscular studies incorporate as an inclusion criterion the patient's agreement not to share any of study experiences through social media with other patients during the study conduct. Consideration of these challenges will allow timely response to the high unmet medical needs for many neuromuscular diseases. PMID:26691331

  7. Assessment of Neuromuscular Function Using Percutaneous Electrical Nerve Stimulation.

    PubMed

    Rozand, Vianney; Grosprêtre, Sidney; Stapley, Paul J; Lepers, Romuald

    2015-09-13

    Percutaneous electrical nerve stimulation is a non-invasive method commonly used to evaluate neuromuscular function from brain to muscle (supra-spinal, spinal and peripheral levels). The present protocol describes how this method can be used to stimulate the posterior tibial nerve that activates plantar flexor muscles. Percutaneous electrical nerve stimulation consists of inducing an electrical stimulus to a motor nerve to evoke a muscular response. Direct (M-wave) and/or indirect (H-reflex) electrophysiological responses can be recorded at rest using surface electromyography. Mechanical (twitch torque) responses can be quantified with a force/torque ergometer. M-wave and twitch torque reflect neuromuscular transmission and excitation-contraction coupling, whereas H-reflex provides an index of spinal excitability. EMG activity and mechanical (superimposed twitch) responses can also be recorded during maximal voluntary contractions to evaluate voluntary activation level. Percutaneous nerve stimulation provides an assessment of neuromuscular function in humans, and is highly beneficial especially for studies evaluating neuromuscular plasticity following acute (fatigue) or chronic (training/detraining) exercise.

  8. Biochemistry of Neuromuscular Diseases: A Course for Undergraduate Students

    ERIC Educational Resources Information Center

    Ohlendieck, Kay

    2002-01-01

    This article outlines an undergraduate course focusing on supramolecular membrane protein complexes involved in the molecular pathogenesis of neuromuscular disorders. The emphasis of this course is to introduce students to the key elements involved in the ion regulation and membrane stabilization during muscle contraction and the role of these…

  9. Neuromuscular activation patterns during treadmill walking after space flight

    NASA Technical Reports Server (NTRS)

    Layne, C. S.; McDonald, P. V.; Bloomberg, J. J.

    1997-01-01

    Astronauts adopt a variety of neuromuscular control strategies during space flight that are appropriate for locomoting in that unique environment, but are less than optimal upon return to Earth. We report here the first systematic investigation of potential adaptations in neuromuscular activity patterns associated with postflight locomotion. Astronaut-subjects were tasked with walking on a treadmill at 6.4 km/h while fixating a visual target 30 cm away from their eyes after space flights of 8-15 days. Surface electromyography was collected from selected lower limb muscles and normalized with regard to mean amplitude and temporal relation to heel strike. In general, high correlations (more than 0.80) were found between preflight and postflight activation waveforms for each muscle and each subject: however relative activation amplitude around heel strike and toe off was changed as a result of flight. The level of muscle cocontraction and activation variability, and the relationship between the phasic characteristics of the ankle musculature in preparation for toe off also were altered by space flight. Subjects also reported oscillopsia during treadmill walking after flight. These findings indicate that, after space flight, the sensory-motor system can generate neuromuscular-activation strategies that permit treadmill walking, but subtle changes in lower-limb neuromuscular activation are present that may contribute to increased lower limb kinematic variability and oscillopsia also present during postflight walking.

  10. Facial rehabilitation: a neuromuscular reeducation, patient-centered approach.

    PubMed

    Vanswearingen, Jessie

    2008-05-01

    Individuals with facial paralysis and distorted facial expressions and movements secondary to a facial neuromotor disorder experience substantial physical, psychological, and social disability. Previously, facial rehabilitation has not been widely available or considered to be of much benefit. An emerging rehabilitation science of neuromuscular reeducation and evidence for the efficacy of facial neuromuscular reeducation, a process of facilitating the return of intended facial movement patterns and eliminating unwanted patterns of facial movement and expression, may provide patients with disorders of facial paralysis or facial movement control opportunity for the recovery of facial movement and function. We provide a brief overview of the scientific rationale for facial neuromuscular reeducation in the structure and function of the facial neuromotor system, the neuropsychology of facial expression, and relations among expressions, movement, and emotion. The primary purpose is to describe principles of neuromuscular reeducation, assessment and outcome measures, approach to treatment, the process, including surface-electromyographic biofeedback as an adjunct to reeducation, and the goal of enhancing the recovery of facial expression and function in a patient-centered approach to facial rehabilitation.

  11. Neuromuscular exercise as treatment of degenerative knee disease.

    PubMed

    Ageberg, Eva; Roos, Ewa M

    2015-01-01

    Exercise is recommended as first-line treatment of degenerative knee disease. Our hypothesis is that neuromuscular exercise is feasible and at least as effective as traditionally used strength or aerobic training but aims to target more closely the sensorimotor deficiencies and functional instability associated with the degenerative knee disease than traditionally used training methods.

  12. Neuromuscular Electrical Stimulation for Mobility Support of Elderly

    PubMed Central

    2015-01-01

    The stimulator for neuromuscular electrical stimulation for mobility support of elderly is not very complicated, but for application within “MOBIL” we have some additional demands to fulfill. First we have specific safety issues for this user group. A powerful compliance management system is crucial not only to guide daily application, but for creating hard data for the scientific outcome. We also need to assure easy handling of the stimulator, because the subjects are generally not able to cope with too difficult and complex motor skills. So, we developed five generations of stimulators and optimizing solutions after field tests. We are already planning the sixth generation with wireless control of the stimulation units by the central main handheld control unit. In a prototype, we have implemented a newly available high capacity memory, a breakthrough in “compliance data storage” as they offer the necessary high storage capacity and fast data handling for an affordable prize. The circuit also contains a 3D accelerometer sensor which acts as a further important safety features: if the control unit drops, this event is detected automatically by the sensor and activates an emergency switch-off that disables the stimulation to avoid associated risks. Further, we have implemented a hardware emergence shutdown and other safety measures. Finally, in the last example muscle torque measurements are referenced with compliance data. In the study normalized maximum voluntary contraction (MVC) and maximum stimulation induced contraction (MSC) were assessed in regular check-ups along the training period. With additional consideration of adjusted stimulation intensity for training out of the compliance data records we are able to estimate the induced contraction strength, which turned out to amount in average 11% of MVC. This value may seem on a first sight rather low, and ought to be considered in relation to the results at the end of the training period. Therefore the

  13. Neuromuscular Electrical Stimulation for Mobility Support of Elderly.

    PubMed

    Mayr, Winfried

    2015-08-24

    The stimulator for neuromuscular electrical stimulation for mobility support of elderly is not very complicated, but for application within "MOBIL" we have some additional demands to fulfill. First we have specific safety issues for this user group. A powerful compliance management system is crucial not only to guide daily application, but for creating hard data for the scientific outcome. We also need to assure easy handling of the stimulator, because the subjects are generally not able to cope with too difficult and complex motor skills. So, we developed five generations of stimulators and optimizing solutions after field tests. We are already planning the sixth generation with wireless control of the stimulation units by the central main handheld control unit. In a prototype, we have implemented a newly available high capacity memory, a breakthrough in "compliance data storage" as they offer the necessary high storage capacity and fast data handling for an affordable prize. The circuit also contains a 3D accelerometer sensor which acts as a further important safety features: if the control unit drops, this event is detected automatically by the sensor and activates an emergency switch-off that disables the stimulation to avoid associated risks. Further, we have implemented a hardware emergence shutdown and other safety measures. Finally, in the last example muscle torque measurements are referenced with compliance data. In the study normalized maximum voluntary contraction (MVC) and maximum stimulation induced contraction (MSC) were assessed in regular check-ups along the training period. With additional consideration of adjusted stimulation intensity for training out of the compliance data records we are able to estimate the induced contraction strength, which turned out to amount in average 11% of MVC. This value may seem on a first sight rather low, and ought to be considered in relation to the results at the end of the training period. Therefore the

  14. Endomicroscopy and electromyography of neuromuscular junctions in situ

    PubMed Central

    Brown, Rosalind; Dissanayake, Kosala N; Skehel, Paul A; Ribchester, Richard R

    2014-01-01

    Objective Electromyography (EMG) is used routinely to diagnose neuromuscular dysfunction in a wide range of peripheral neuropathies, myopathies, and neuromuscular degenerative diseases including motor neuron diseases such as amyotrophic lateral sclerosis (ALS). Definitive neurological diagnosis may also be indicated by the analysis of pathological neuromuscular innervation in motor-point biopsies. Our objective in this study was to preempt motor-point biopsy by combining live imaging with electrophysiological analysis of slow degeneration of neuromuscular junctions (NMJs) in vivo. Methods We combined conventional needle electromyography with fiber-optic confocal endomicroscopy (CEM), using an integrated hand-held, 1.5-mm-diameter probe. We utilized as a test bed, various axotomized muscles in the hind limbs of anaesthetized, double-homozygous thy1.2YFP16: WldS mice, which coexpress the Wallerian-degeneration Slow (WldS) protein and yellow fluorescent protein (YFP) in motor neurons. We also tested exogenous vital stains, including Alexa488-α-bungarotoxin; the styryl pyridinium dye 4-Di-2-Asp; and a GFP conjugate of botulinum toxin Type A heavy chain (GFP-HcBoNT/A). Results We show that an integrated EMG/CEM probe is effective in longitudinal evaluation of functional and morphological changes that take place over a 7-day period during axotomy-induced, slow neuromuscular synaptic degeneration. EMG amplitude declined in parallel with overt degeneration of motor nerve terminals. EMG/CEM was safe and effective when nerve terminals and motor endplates were selectively stained with vital dyes. Interpretation Our findings constitute proof-of-concept, based on live imaging in an animal model, that combining EMG/CEM may be useful as a minimally invasive precursor or alternative to motor-point biopsy in neurological diagnosis and for monitoring local administration of potential therapeutics. PMID:25540801

  15. Neuromuscular Activity of Micrurus laticollaris (Squamata: Elapidae) Venom in Vitro

    PubMed Central

    Carbajal-Saucedo, Alejandro; Floriano, Rafael Stuani; Dal Belo, Cháriston André; Olvera-Rodríguez, Alejandro; Alagón, Alejandro; Rodrigues-Simioni, Léa

    2014-01-01

    In this work, we have examined the neuromuscular activity of Micrurus laticollaris (Mexican coral snake) venom (MLV) in vertebrate isolated nerve-muscle preparations. In chick biventer cervicis preparations, the MLV induced an irreversible concentration- and time-dependent (1–30 µg/mL) neuromuscular blockade, with 50% blockade occurring between 8 and 30 min. Muscle contractures evoked by exogenous acetylcholine were completely abolished by MLV, whereas those of KCl were also significantly altered (86% ± 11%, 53% ± 11%, 89% ± 5% and 89% ± 7% for one, three, 10 and 30 µg of venom/mL, respectively; n = 4; p < 0.05). In mouse phrenic nerve-diaphragm preparations, MLV (1–10 µg/mL) promoted a slight increase in the amplitude of twitch-tension (3 µg/mL), followed by neuromuscular blockade (n = 4); the highest concentration caused complete inhibition of the twitches (time for 50% blockade = 26 ± 3 min), without exhibiting a previous neuromuscular facilitation. The venom (3 µg/mL) induced a biphasic modulation in the frequency of miniature end-plate potentials (MEPPs)/min, causing a significant increase after 15 min, followed by a decrease after 60 min (from 17 ± 1.4 (basal) to 28 ± 2.5 (t15) and 12 ± 2 (t60)). The membrane resting potential of mouse diaphragm preparations pre-exposed or not to d-tubocurarine (5 µg/mL) was also significantly less negative with MLV (10 µg/mL). Together, these results indicate that M. laticollaris venom induces neuromuscular blockade by a combination of pre- and post-synaptic activities. PMID:24445448

  16. Neuromuscular activity of Micrurus laticollaris (Squamata: Elapidae) venom in vitro.

    PubMed

    Carbajal-Saucedo, Alejandro; Floriano, Rafael Stuani; Dal Belo, Cháriston André; Olvera-Rodríguez, Alejandro; Alagón, Alejandro; Rodrigues-Simioni, Léa

    2014-01-17

    In this work, we have examined the neuromuscular activity of Micrurus laticollaris (Mexican coral snake) venom (MLV) in vertebrate isolated nerve-muscle preparations. In chick biventer cervicis preparations, the MLV induced an irreversible concentration- and time-dependent (1-30 µg/mL) neuromuscular blockade, with 50% blockade occurring between 8 and 30 min. Muscle contractures evoked by exogenous acetylcholine were completely abolished by MLV, whereas those of KCl were also significantly altered (86% ± 11%, 53% ± 11%, 89% ± 5% and 89% ± 7% for one, three, 10 and 30 µg of venom/mL, respectively; n = 4; p < 0.05). In mouse phrenic nerve-diaphragm preparations, MLV (1-10 µg/mL) promoted a slight increase in the amplitude of twitch-tension (3 µg/mL), followed by neuromuscular blockade (n = 4); the highest concentration caused complete inhibition of the twitches (time for 50% blockade = 26 ± 3 min), without exhibiting a previous neuromuscular facilitation. The venom (3 µg/mL) induced a biphasic modulation in the frequency of miniature end-plate potentials (MEPPs)/min, causing a significant increase after 15 min, followed by a decrease after 60 min (from 17 ± 1.4 (basal) to 28 ± 2.5 (t15) and 12 ± 2 (t60)). The membrane resting potential of mouse diaphragm preparations pre-exposed or not to d-tubocurarine (5 µg/mL) was also significantly less negative with MLV (10 µg/mL). Together, these results indicate that M. laticollaris venom induces neuromuscular blockade by a combination of pre- and post-synaptic activities.

  17. [The effect of atropine and diazepam on mammalian neuromuscular junction--a model of their protective action against anticholinesterase-based war and agriculture poisons].

    PubMed

    Vyskocil, Frantisek

    2006-01-01

    The effect of atropine and diazepam on the mammalian neuromuscular junction. Nicotinolytic effect of atropine on the neuromuscular junction is discussed as a main mechanism of the beneficial effect of this drug during war and agriculture poisoning by anticholinesterases. Atropine is beneficial as it reduces the amplitude of intracellularly recorded endplate potentials and, first of all, causes a marked shortening of their time course (Beránek, Vyskocil 1968, Magazanik, Vyskocil 1969). Diazepam effectively blocks trains of action potentials in individual rat diaphragm muscle fibers, apparently by elevating the chloride permeability. It is suggested that similar increase in Cl- permeability may occur in brain excitable structures and can counteract the anticholinesterase-induced prolongation of ACh-depolarization that evokes repetitive firing.

  18. Vellozia flavicans Mart. ex Schult. hydroalcoholic extract inhibits the neuromuscular blockade induced by Bothrops jararacussu venom

    PubMed Central

    2014-01-01

    Background Snakebite is a significant public health issue in tropical countries. In Brazil, some of the most common snake envenomations are from Bothrops. Bothrops bites trigger local and systemic effects including edema, pain, erythema, cyanosis, infections, and necrosis. Vellozia flavicans is a plant from the Brazilian “cerrado” (savanna) that is popularly used as an anti-inflammatory medicine. Since inflammation develops quickly after Bothrops bites, which can lead to infection, the aim of the present study was to observe possible anti-snake venom and antimicrobial activities of V. flavicans (Vf). Methods The chromatographic profile of the main constituents from the Vf leaf hydroalcoholic extract was obtained by thin-layer chromatography (TLC). The anti-snake venom activity was measured by Vf’s ability to neutralize the in vitro neuromuscular blockade caused by Bothrops jararacussu venom (Bjssu) in a mouse phrenic nerve-diaphragm model (PND). After a 20 min incubation, preparations of PND were added to Tyrode’s solution (control); Vf (0.2, 0.5, 1, and 2 mg/mL); 40 μg/mL Bjssu; pre-incubation for 30 min with Bjssu and 1 mg/mL Vf; and a Bjssu pretreated preparation (for 10 min) followed by 1 mg/mL Vf. Myographic recording was performed, and the contractile responses were recorded. The antimicrobial activity (minimum inhibitory concentration [MIC] and minimum bactericidal concentration [MBC]) was obtained for Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecalis, using gentamicin and vancomycin as positive controls. Results TLC analysis yielded several compounds from Vf, such as flavonoids (quercetin) and phenolic acids (chlorogenic acid). Bjssu completely blocked the contractile responses of PND preparations, while Vf preserved 97% (±10%) of the contractile responses when incubated with Bjssu. In the PND pretreated with Bjssu, Vf was able to inhibit the neuromuscular blockade progress. MIC and MBC of Vf ranged

  19. Treatment of pyridostigmine-induced AV block with hyoscyamine in a patient with myasthenia gravis.

    PubMed

    Gehi, Anil; Benatar, Michael; Langberg, Jonathan

    2008-02-01

    Myasthenia gravis is an autoimmune disorder of the nervous system typically mediated by antibodies against the nicotinic acetylcholine receptor at the neuromuscular junction. Treatment of myasthenia gravis frequently involves the use of cholinesterase inhibitors such as pyridostigmine. Treatment with these agents has been associated with bradycardia and syncope requiring pacemaker implantation. We report a case of a 60-year-old man with a 1-year history of myasthenia gravis treated with pyridostigmine who presented with syncope due to high degree AV block. Before committing the patient to a permanent pacemaker, a trial of medical therapy with hyoscyamine was attempted. Hyoscyamine is a muscarinic antagonist commonly used to block cholinergic side effects associated with pyridostigmine without reducing its efficacy at the neuromuscular junction. Treatment with hyoscyamine resulted in complete resolution of AV block, thereby avoiding pacemaker implantation.

  20. Recovery of mouse neuromuscular junctions from single and repeated injections of botulinum neurotoxin A

    PubMed Central

    Rogozhin, A A; Pang, K K; Bukharaeva, E; Young, C; Slater, C R

    2008-01-01

    Botulinum neurotoxin type A (BoNT/A) paralyses muscles by blocking acetylcholine (ACh) release from motor nerve terminals. Although highly toxic, it is used clinically to weaken muscles whose contraction is undesirable, as in dystonias. The effects of an injection of BoNT/A wear off after 3–4 months so repeated injections are often used. Recovery of neuromuscular transmission is accompanied by the formation of motor axon sprouts, some of which form new synaptic contacts. However, the functional importance of these new contacts is unknown. Using intracellular and focal extracellular recording we show that in the mouse epitrochleoanconeus (ETA), quantal release from the region of the original neuromuscular junction (NMJ) can be detected as soon as from new synaptic contacts, and generally accounts for > 80% of total release. During recovery the synaptic delay and the rise and decay times of endplate potentials (EPPs) become prolonged approximately 3-fold, but return to normal after 2–3 months. When studied after 3–4 months, the response to repetitive stimulation at frequencies up to 100 Hz is normal. When two or three injections of BoNT/A are given at intervals of 3–4 months, quantal release returns to normal values more slowly than after a single injection (11 and 15 weeks to reach 50% of control values versus 6 weeks after a single injection). In addition, branching of the intramuscular muscular motor axons, the distribution of the NMJs and the structure of many individual NMJs remain abnormal. These findings highlight the plasticity of the mammalian NMJ but also suggest important limits to it. PMID:18467364

  1. The Onecut Transcription Factor HNF-6 Regulates in Motor Neurons the Formation of the Neuromuscular Junctions

    PubMed Central

    Audouard, Emilie; Schakman, Olivier; René, Frédérique; Huettl, Rosa-Eva; Huber, Andrea B.; Loeffler, Jean-Philippe; Gailly, Philippe; Clotman, Frédéric

    2012-01-01

    The neuromuscular junctions are the specialized synapses whereby spinal motor neurons control the contraction of skeletal muscles. The formation of the neuromuscular junctions is controlled by a complex interplay of multiple mechanisms coordinately activated in motor nerve terminals and in their target myotubes. However, the transcriptional regulators that control in motor neurons the genetic programs involved in neuromuscular junction development remain unknown. Here, we provide evidence that the Onecut transcription factor HNF-6 regulates in motor neurons the formation of the neuromuscular junctions. Indeed, adult Hnf6 mutant mice exhibit hindlimb muscle weakness and abnormal locomotion. This results from defects of hindlimb neuromuscular junctions characterized by an abnormal morphology and defective localization of the synaptic vesicle protein synaptophysin at the motor nerve terminals. These defects are consequences of altered and delayed formation of the neuromuscular junctions in newborn mutant animals. Furthermore, we show that the expression level of numerous regulators of neuromuscular junction formation, namely agrin, neuregulin-2 and TGF-ß receptor II, is downregulated in the spinal motor neurons of Hnf6 mutant newborn animals. Finally, altered formation of neuromuscular junction-like structures in a co-culture model of wildtype myotubes with mutant embryonic spinal cord slices is rescued by recombinant agrin and neuregulin, indicating that depletion in these factors contributes to defective neuromuscular junction development in the absence of HNF-6. Thus, HNF-6 controls in spinal motor neurons a genetic program that coordinates the formation of hindlimb neuromuscular junctions. PMID:23227180

  2. [Neuromuscular disease: respiratory clinical assessment and follow-up].

    PubMed

    Martínez Carrasco, C; Villa Asensi, J R; Luna Paredes, M C; Osona Rodríguez de Torres, F B; Peña Zarza, J A; Larramona Carrera, H; Costa Colomer, J

    2014-10-01

    Patients with neuromuscular disease are an important group at risk of frequently suffering acute or chronic respiratory failure, which is their main cause of death. They require follow-up by a pediatric respiratory medicine specialist from birth or diagnosis in order to confirm the diagnosis and treat any respiratory complications within a multidisciplinary context. The ventilatory support and the cough assistance have improved the quality of life and long-term survival for many of these patients. In this paper, the authors review the pathophysiology, respiratory function evaluation, sleep disorders, and the most frequent respiratory complications in neuromuscular diseases. The various treatments used, from a respiratory medicine point of view, will be analyzed in a next paper.

  3. The ageing neuromuscular system and sarcopenia: a mitochondrial perspective

    PubMed Central

    Picard, Martin; Turnbull, Doug M.

    2016-01-01

    Abstract Skeletal muscles undergo structural and functional decline with ageing, culminating in sarcopenia. The underlying neuromuscular mechanisms have been the subject of intense investigation, revealing mitochondrial abnormalities as potential culprits within both nerve and muscle cells. Implicated mechanisms involve impaired mitochondrial dynamics, reduced organelle biogenesis and quality control via mitophagy, accumulation of mitochondrial DNA (mtDNA) damage and respiratory chain defect, metabolic disturbance, pro‐apoptotic signalling, and oxidative stress. This article provides an overview of the cellular mechanisms whereby mitochondria may promote maladaptive changes within motor neurons, the neuromuscular junction (NMJ) and muscle fibres. Lifelong physical activity, which promotes mitochondrial health across tissues, is emerging as an effective countermeasure for sarcopenia. PMID:26921061

  4. An overview of neurological and neuromuscular signs in mitochondrial diseases.

    PubMed

    Chaussenot, A; Paquis-Flucklinger, V

    2014-05-01

    Mitochondrial disorders have a broad clinical spectrum and are genetically heterogeneous, involving two genomes. These disorders may be develop at any age, with isolated or multiple system involvement, and any pattern of inheritance. Neurological involvement is the most frequent, and concerns muscular, peripheral and central nervous system. Among these diverse signs, some are suggestive of mitochondrial disease, such as progressive external ophthalmoplegia, exercise intolerance, psychomotor regression, stroke-like episodes, refractory epilepsy and Epilepsia Partialis Continua. Others are less specific and mitochondrial hypothesis may be evocated because of either association of different neuromuscular signs or a multisystemic involvement. This review describes the wealth of this neurological and neuromuscular symptomatology through different syndromes reported in the literature, according to preponderant signs and to modes of inheritance, as key elements to guide genetics testing.

  5. The role of neuromuscular inhibition in hamstring strain injury recurrence.

    PubMed

    Fyfe, Jackson J; Opar, David A; Williams, Morgan D; Shield, Anthony J

    2013-06-01

    Hamstring strain injuries are amongst the most common and problematic injuries in a wide range of sports that involve high speed running. The comparatively high rate of hamstring injury recurrence is arguably the most concerning aspect of these injuries. A number of modifiable and nonmodifiable risk factors are proposed to predispose athletes to hamstring strains. Potentially, the persistence of risk factors and the development of maladaptations following injury may explain injury recurrence. Here, the role of neuromuscular inhibition following injury is discussed as a potential mechanism for several maladaptations associated with hamstring re-injury. These maladaptations include eccentric hamstring weakness, selective hamstring atrophy and shifts in the knee flexor torque-joint angle relationship. Current evidence indicates that athletes return to competition after hamstring injury having developed maladaptations that predispose them to further injury. When rehabilitating athletes to return to competition following hamstring strain injury, the role of neuromuscular inhibition in re-injury should be considered.

  6. Neuromuscular deficits after peripheral joint injury: a neurophysiological hypothesis.

    PubMed

    Ward, Sarah; Pearce, Alan J; Pietrosimone, Brian; Bennell, Kim; Clark, Ross; Bryant, Adam L

    2015-03-01

    In addition to biomechanical disturbances, peripheral joint injuries (PJIs) can also result in chronic neuromuscular alterations due in part to loss of mechanoreceptor-mediated afferent feedback. An emerging perspective is that PJI should be viewed as a neurophysiological dysfunction, not simply a local injury. Neurophysiological and neuroimaging studies have provided some evidence for central nervous system (CNS) reorganization at both the cortical and spinal levels after PJI. The novel hypothesis proposed is that CNS reorganization is the underlying mechanism for persisting neuromuscular deficits after injury, particularly muscle weakness. There is a lack of direct evidence to support this hypothesis, but future studies utilizing force-matching tasks with superimposed transcranial magnetic stimulation may be help clarify this notion.

  7. [Neuromuscular disease: respiratory clinical assessment and follow-up].

    PubMed

    Martínez Carrasco, C; Villa Asensi, J R; Luna Paredes, M C; Osona Rodríguez de Torres, F B; Peña Zarza, J A; Larramona Carrera, H; Costa Colomer, J

    2014-10-01

    Patients with neuromuscular disease are an important group at risk of frequently suffering acute or chronic respiratory failure, which is their main cause of death. They require follow-up by a pediatric respiratory medicine specialist from birth or diagnosis in order to confirm the diagnosis and treat any respiratory complications within a multidisciplinary context. The ventilatory support and the cough assistance have improved the quality of life and long-term survival for many of these patients. In this paper, the authors review the pathophysiology, respiratory function evaluation, sleep disorders, and the most frequent respiratory complications in neuromuscular diseases. The various treatments used, from a respiratory medicine point of view, will be analyzed in a next paper. PMID:24709048

  8. Aggravated neuromuscular symptoms of mercury exposure from dental amalgam fillings.

    PubMed

    Akbal, Ayla; Yılmaz, Hınç; Tutkun, Engin; Köş, Durdu Mehmet

    2014-01-01

    Dental amalgam fillings are widely used all over the world. However, their mercury content can lead to various side effects and clinical problems. Acute or chronic mercury exposure can cause several side effects on the central nerve system, renal and hepatic functions, immune system, fetal development and it can play a role on exacerbation of neuromuscular diseases. In this case, we will present a patient with vacuolar myopathy whose symptoms were started and aggravated with her dental amalgam fillings.

  9. Report on Adaptive Force, A Specific Neuromuscular Function.

    PubMed

    Hoff, Marko; Schaefer, Laura; Heinke, Nancy; Bittmann, Frank

    2015-09-11

    In real life motions, as well as in sports, the adaptation of the neuromuscular systems to externally applied forces plays an important role. The term Adaptive Force (AF) shall characterize the ability of the nerve-muscle-system to adapt to impacting external forces during isometric and eccentric muscle action. The focus in this paper is on the concept of this neuromuscular action, which is not yet described in this way. A measuring system was constructed and evaluated for this specific neuromuscular function, but only the main information of the evaluation of the measuring system and the preliminary reference values are mentioned here, while an article with detailed description will be published separately. This paper concentrates on the three following points: 1) What is the peculiarity of this neuromuscular function, introduced as AF? 2) Is the measuring system able to capture its specific characteristics and which phases of measurement occur? 3) It seems reasonable to discuss if AF can be distinguished and classified among the known force concepts. The article describes the measuring system and how it is able to capture special features of real life motions like submaximal intensities and the subjects' option to react adequately on external varying forces. Furthermore, within one measurement the system records three different force qualities: the isometric submaximal Adaptive Force (AFiso), the maximal isometric Adaptive Force (AFisomax) and the maximal eccentric Adaptive Force (AFeccmax). Each of these phases provide different and unique information on the nerve-muscle-system that are discussed in detail. Important, in terms of the Adaptive Force, seems to be the combination of conditional and coordinative abilities. This project was funded by the Federal Ministry of Economy and Technology (Project ZIM KF2262301FO9). PMID:26913155

  10. An Overview of Cardiac Management in Neuromuscular Disease.

    PubMed

    Hickey, Renee M; Cullen, John D; Sachs, George M

    2016-01-01

    Muscular dystrophy and myasthenia gravis are two neuromuscular disorders that can involve significant cardiovascular complications. The frequency and severity of cardiac pathology varies widely among the muscular dystrophies. In some, it is nearly inevitable and requires regular evaluation. In others, assessment of cardiac function can be more symptom-driven. On-ly a minority of myasthenic patients manifest disease-related cardiovascular complications; however, their presentation can be rapidly progressive and life-threatening.. PMID:27347224

  11. An Overview of Cardiac Management in Neuromuscular Disease

    PubMed Central

    Hickey, Renee M.; Cullen, John D.; Sachs, George M.

    2016-01-01

    Muscular dystrophy and myasthenia gravis are two neuromuscular disorders that can involve significant cardiovascular complications. The frequency and severity of cardiac pathology varies widely among the muscular dystrophies. In some, it is nearly inevitable and requires regular evaluation. In others, assessment of cardiac function can be more symptom-driven. On-ly a minority of myasthenic patients manifest disease-related cardiovascular complications; however, their presentation can be rapidly progressive and life-threatening.. PMID:27347224

  12. Neuromuscular electric stimulation in patellofemoral dysfunction: literature review

    PubMed Central

    dos Santos, Ricardo Lucas; Souza, Márcia Leal São Pedro; dos Santos, Fernanda Andrade

    2013-01-01

    Patellofemoral dysfunction is a fairly common deficiency among young individuals that primarily affects females and may be characterized by pain, swelling and retropatellar crepitation. The purpose of this review of literature from the period between 2005 and 2011 was to systematize knowledge in relation to the increase in quadriceps muscle strength and pain relief in patients with patellofemoral dysfunction, using neuromuscular electrical stimulation and resistance exercises. The inclusion criteria were intervention articles from the past six years, in English, Spanish and Portuguese, which used muscle strengthening and neuromuscular electrical stimulation for rehabilitation obtained through searches in the electronic databases Medline and Lilacs and in the Bireme library. The bibliographic search yielded 28 references, of which nine were excluded in accordance with the aims and inclusion criteria while 16 articles were selected for reading of the abstracts and subsequent analysis. Mediumfrequency Neuromuscular Electrical Stimulation (NMES) can be used in association with resistance exercises as an adjuvant in the treatment of patellofemoral dysfunction (PFD), both to achieve muscle rebalance and for pain relief. PMID:24453645

  13. A biodynamic feedthrough model based on neuromuscular principles.

    PubMed

    Venrooij, Joost; Abbink, David A; Mulder, Mark; van Paassen, Marinus M; Mulder, Max; van der Helm, Frans C T; Bulthoff, Heinrich H

    2014-07-01

    A biodynamic feedthrough (BDFT) model is proposed that describes how vehicle accelerations feed through the human body, causing involuntary limb motions and so involuntary control inputs. BDFT dynamics strongly depend on limb dynamics, which can vary between persons (between-subject variability), but also within one person over time, e.g., due to the control task performed (within-subject variability). The proposed BDFT model is based on physical neuromuscular principles and is derived from an established admittance model-describing limb dynamics-which was extended to include control device dynamics and account for acceleration effects. The resulting BDFT model serves primarily the purpose of increasing the understanding of the relationship between neuromuscular admittance and biodynamic feedthrough. An added advantage of the proposed model is that its parameters can be estimated using a two-stage approach, making the parameter estimation more robust, as the procedure is largely based on the well documented procedure required for the admittance model. To estimate the parameter values of the BDFT model, data are used from an experiment in which both neuromuscular admittance and biodynamic feedthrough are measured. The quality of the BDFT model is evaluated in the frequency and time domain. Results provide strong evidence that the BDFT model and the proposed method of parameter estimation put forward in this paper allows for accurate BDFT modeling across different subjects (accounting for between-subject variability) and across control tasks (accounting for within-subject variability).

  14. Neuromuscular signs associated with acute hypophosphatemia in a dog.

    PubMed

    Claus, Kimberly N; Day, Thomas K; Wolf, Christina

    2015-01-01

    The purpose of this report was to describe the successful recognition and management of neuromuscular dysfunction secondary to severe, acute hypophosphatemia in an adult dog with a 2 day history of vomiting, anorexia, and abdominal pain. Radiographs were suggestive of a foreign body obstruction, and surgery was recommended. Resection and anastomosis of the distal duodenum and proximal jejunum was performed. The dog recovered uneventfully, but approximately 36 hr postoperatively, he was found to have significant weakness and muscle tremors that were accompanied by hyperthermia. The only significant abnormality on a serum biochemical profile was a phosphorous level of 0.26 mmol/L. Within 6 hr of initiating phosphorous supplementation, the patient fully recovered and had no residual signs of neuromuscular dysfunction. Signs of neurologic dysfunction secondary to hypophosphatemia are commonly recognized in human patients. Reports of patients with severe muscle weakness, some of which necessitate ventilation due to weakening of muscles of respiration, are common throughout the literature. Less commonly, tremors are noted. This is the first known report of neuromuscular signs recognized and rapidly corrected in a dog. Although it is likely to be uncommon, hypophosphatemia should be recognized as a differential diagnosis in patients with tremors and/or muscle weakness. PMID:25955140

  15. Altered neuromuscular control mechanisms of the trapezius muscle in fibromyalgia

    PubMed Central

    2010-01-01

    Background fibromyalgia is a relatively common condition with widespread pain and pressure allodynia, but unknown aetiology. For decades, the association between motor control strategies and chronic pain has been a topic for debate. One long held functional neuromuscular control mechanism is differential activation between regions within a single muscle. The aim of this study was to investigate differences in neuromuscular control, i.e. differential activation, between myalgic trapezius in fibromyalgia patients and healthy controls. Methods 27 fibromyalgia patients and 30 healthy controls performed 3 minutes bilateral shoulder elevations with different loads (0-4 Kg) with a high-density surface electromyographical (EMG) grid placed above the upper trapezius. Differential activation was quantified by the power spectral median frequency of the difference in EMG amplitude between the cranial and caudal parts of the upper trapezius. The average duration of the differential activation was described by the inverse of the median frequency of the differential activations. Results the median frequency of the differential activations was significantly lower, and the average duration of the differential activations significantly longer in fibromyalgia compared with controls at the two lowest load levels (0-1 Kg) (p < 0.04), but not at the two highest load levels (2 and 4 Kg). Conclusion these findings illustrate a different neuromuscular control between fibromyalgia patients and healthy controls during a low load functional task, either sustaining or resulting from the chronic painful condition. The findings may have clinical relevance for rehabilitation strategies for fibromyalgia. PMID:20205731

  16. Neuromuscular interactions around the knee in children, adults and elderly

    PubMed Central

    Kellis, Eleftherios; Mademli, Lida; Patikas, Dimitrios; Kofotolis, Nikolaos

    2014-01-01

    Although injury and neuromuscular activation patterns may be common for all individuals, there are certain factors which differentiate neuromuscular activity responses between children, adults and elderly. The purpose of this study is to review recent evidence on age differences in neural activation and muscle balances around the knee when performing single joint movements. Particularly, current evidence indicates that there are some interesting similarities in the neuromuscular mechanisms by which children or the elderly differ compared with adults. Both children and elderly display a lower absolute muscle strength capacity than adults which cannot fully be explained by differences in muscle mass. Quadriceps activation failure is a common symptom of all knee injuries, irrespective of age but it is likely that its effect is more evident in children or adults. While one might expect that antagonist co-activation would differ between age categories, it appears that this is not the case. Although hamstring: quadriceps ratio levels are altered after knee injury, it is not clear whether this is an age specific response. Finally, evidence suggests that both children and the elderly display less stiffness of the quadriceps muscle-tendon unit than adults which affects their knee joint function. PMID:25232523

  17. Neuromuscular signs associated with acute hypophosphatemia in a dog.

    PubMed

    Claus, Kimberly N; Day, Thomas K; Wolf, Christina

    2015-01-01

    The purpose of this report was to describe the successful recognition and management of neuromuscular dysfunction secondary to severe, acute hypophosphatemia in an adult dog with a 2 day history of vomiting, anorexia, and abdominal pain. Radiographs were suggestive of a foreign body obstruction, and surgery was recommended. Resection and anastomosis of the distal duodenum and proximal jejunum was performed. The dog recovered uneventfully, but approximately 36 hr postoperatively, he was found to have significant weakness and muscle tremors that were accompanied by hyperthermia. The only significant abnormality on a serum biochemical profile was a phosphorous level of 0.26 mmol/L. Within 6 hr of initiating phosphorous supplementation, the patient fully recovered and had no residual signs of neuromuscular dysfunction. Signs of neurologic dysfunction secondary to hypophosphatemia are commonly recognized in human patients. Reports of patients with severe muscle weakness, some of which necessitate ventilation due to weakening of muscles of respiration, are common throughout the literature. Less commonly, tremors are noted. This is the first known report of neuromuscular signs recognized and rapidly corrected in a dog. Although it is likely to be uncommon, hypophosphatemia should be recognized as a differential diagnosis in patients with tremors and/or muscle weakness.

  18. Methods for Multiloop Identification of Visual and Neuromuscular Pilot Responses.

    PubMed

    Olivari, Mario; Nieuwenhuizen, Frank M; Venrooij, Joost; Bülthoff, Heinrich H; Pollini, Lorenzo

    2015-12-01

    In this paper, identification methods are proposed to estimate the neuromuscular and visual responses of a multiloop pilot model. A conventional and widely used technique for simultaneous identification of the neuromuscular and visual systems makes use of cross-spectral density estimates. This paper shows that this technique requires a specific noninterference hypothesis, often implicitly assumed, that may be difficult to meet during actual experimental designs. A mathematical justification of the necessity of the noninterference hypothesis is given. Furthermore, two methods are proposed that do not have the same limitations. The first method is based on autoregressive models with exogenous inputs, whereas the second one combines cross-spectral estimators with interpolation in the frequency domain. The two identification methods are validated by offline simulations and contrasted to the classic method. The results reveal that the classic method fails when the noninterference hypothesis is not fulfilled; on the contrary, the two proposed techniques give reliable estimates. Finally, the three identification methods are applied to experimental data from a closed-loop control task with pilots. The two proposed techniques give comparable estimates, different from those obtained by the classic method. The differences match those found with the simulations. Thus, the two identification methods provide a good alternative to the classic method and make it possible to simultaneously estimate human's neuromuscular and visual responses in cases where the classic method fails.

  19. Fatty replacement of lower paraspinal muscles: normal and neuromuscular disorders

    SciTech Connect

    Hader, H.; Gadoth, N.; Heifetz, H.

    1983-11-01

    The physiologic replacement of the lower paraspinal muscles by fat was evaluated in 157 patients undergoing computed tomography for reasons unrelated to abnormalities of the locomotor system. Five patients with neuromuscular disorders were similarly evaluated. The changes were graded according to severity at three spinal levels: lower thoracic-upper lumbar, midlumbar, and lumbosacral. The results were analyzed in relation to age and gender. It was found that fatty replacement of paraspinal muscles is a normal age-progressive phenomenon most prominent in females. It progresses down the spine, being most advanced in the lumbosacral region. The severest changes in the five patients with neuromuscular disorders (three with poliomyelitis and two with progressive muscular dystrophy) consisted of complete muscle group replacement by fat. In postpoliomyelitis atrophy, the distribution was typically asymmetric and sometimes lacked clinical correlation. In muscular dystrophy, fatty replacement was symmetric, showing relative sparing of the psoas and multifidus muscles. In patients with neuromuscular diseases, computed tomography of muscles may be helpful in planning a better rehabilitation regimen.

  20. [Molecular mechanisms underlying the formation of neuromuscular junction].

    PubMed

    Higuchi, Osamu; Yamanashi, Yuji

    2011-07-01

    The neuromuscular junction (NMJ) is a synapse between a motor neuron and skeletal muscle. The contraction of skeletal muscle is controlled by the neurotransmitter acetylcholine (ACh), which is released from the motor nerve terminal. To achieve efficient neuromuscular transmission, acetylcholine receptors (AChRs) must be densely clustered on the muscle membrane of the NMJ. Failure of AChR clustering is associated with disorders of neuromuscular transmission such as congenital myasthenic syndromes (CMS) and myasthenia gravis (MG). Motoneuronal agrin and muscle-specific receptor tyrosine kinase (MuSK) are known to play essential roles in the formation and maintenance of NMJs in the central region of each muscle. However, it had been unclear how agrin activates MuSK. Recent studies have elucidated the roles of several key molecules, including the cytoplasmic adaptor protein Dok-7 and LDL receptor-related protein 4 (Lrp4), in agrin-induced MuSK activation. Moreover, new evidence indicates that cyclin-dependent kinase 5 (Cdk5) regulates postsynaptic differentiation. In this review, we summarize the latest developments in molecular mechanisms underlying NMJ formation in vertebrates. PMID:21747134

  1. Age-associated alterations of the neuromuscular junction.

    PubMed

    Jang, Youngmok C; Van Remmen, Holly

    2011-01-01

    Age-related loss of muscle mass and function greatly affects quality of life in the elderly population. Several hypotheses have been proposed but accumulating evidence point to alterations in neuromuscular system during aging as a key event that leads to functional denervation, muscle wasting, and weakness. Over the past few decades, age-associated degeneration of the neuromuscular junction (NMJ) and its components have been well documented. With advancing age, pre-terminal portions of motor axons exhibit regions of abnormal thinning, distension, and sprouting whereas postsynaptic endplates decrease in size and reduce in number, length, and density of postsynaptic folds. Although the exact underlying mechanisms are still lacking, recent studies provided direct evidence that age-associated increase in oxidative stress plays a crucial role in NMJ degeneration and progression of sarcopenia. Homozygous deletion of an important antioxidant enzyme, Cu,Zn superoxide dismutase (CuZnSOD, SOD1) leads to acceleration of age-dependent muscle atrophy, with a significant NMJ degeneration similar to that seen in old wild-type sarcopenic animals. In this short review, we briefly summarize the current understanding of some of the cellular and molecular changes in the NMJ during aging and suggest a role for oxidative stress and mitochondrial dysfunction in age-related changes in the maintenance of neuromuscular innervation.

  2. Guidelines for ethical behavior relating to clinical practice issues in neuromuscular and electrodiagnostic medicine.

    PubMed

    Abel, Naomi A; De Sousa, Eduardo A; Govindarajan, Raghav; Mayer, Matthew P; Simpson, David A

    2015-12-01

    The American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) developed guidelines to formalize the ethical standards that neuromuscular and electrodiagnostic (EDx) physicians should observe in their clinical and scientific activities. Neuromuscular and EDx medicine is a subspecialty of medicine that focuses on evaluation, diagnosis, and comprehensive medical management, including rehabilitation of individuals with neuromuscular disorders. Physicians working in this subspecialty focus on disorders of the motor unit, including muscle, neuromuscular junction, axon, plexus, nerve root, anterior horn cell, and the peripheral nerves (motor and sensory). The neuromuscular and EDx physician's goal is to diagnose and treat these conditions to mitigate their impact and improve the patient's quality of life. The guidelines are consistent with the Principles of Medical Ethics adopted by the American Medical Association and represent a revision of previous AANEM guidelines.

  3. Block Grants: Federal Data Collection Provisions.

    ERIC Educational Resources Information Center

    General Accounting Office, Washington, DC. Div. of Human Resources.

    This fact sheet compares statutory data collection and reporting provisions of the federal education block grant (chapter 2 of the Education Consolidation and Improvement Act of 1981) with the nine other block grant programs funded in fiscal year 1986; data on statutory administrative cost limits are also provided. Each grant's legislation was…

  4. Same-day physical therapy consults in an outpatient neuromuscular disease physician clinic

    PubMed Central

    Pucillo, Evan M; Christensen-Mayer, Nancy; Poole, Shelly D; Whitten, Denise M; Freeman, Danielle; Bohe, Blake R; Swensen, Brandon R; Smith, A Gordon; Johnson, Nicholas E

    2016-01-01

    Background Team-based care has been shown to offer more comprehensive benefits to patients when compared to standard physician-based care alone in clinics for chronic conditions. However, apart from grant-funded multidisciplinary clinics, there are no reports on the usage of same-day physical therapy (PT) consults within a daily outpatient neuromuscular disease (NMD) physician clinic. Objective To determine the impact of same-day PT consults at the University of Utah’s outpatient Clinical Neurosciences Center. Design A qualitative assessment and survey of patient satisfaction. Methods An eight question Health Insurance Portability and Accountability Act-compliant patient satisfaction survey using a 5-point Likert scale was administered. Demographic data and Press-Ganey Provider Satisfaction surveys were retrospectively collected from electronic medical records for patients receiving same-day PT encounters in the neuromuscular division over 1 year. Results Mean (standard deviation) age was 54.22 (19.81) years for 134 patient encounters, median age was 60 years, with 76 male (57%) and 58 female (43%) patients. Mean Likert score for 61 self-reported patient satisfaction surveys for same-day PT consults was 4.87 (97.4%). Press-Ganey Provider Satisfaction scores improved from 89.9% (N=287) for the year prior to 90.8% (N=320) for the corresponding year (P=0.427). A total of 46 (75.4%) patients have either never before received PT care or never before received PT care for their NMD, 67.4% of whom were male. Conclusion Same-day PT consults in an outpatient NMD physician clinic demonstrated excellent patient satisfaction and improved access to specialty care. This model could potentially be implemented in other academic medical centers to improve access to rehabilitation services for patients with NMD. PMID:27757040

  5. Ethical considerations in the management of individuals with severe neuromuscular disorders.

    PubMed

    Bach, J R; Barnett, V

    1994-04-01

    There have been many recent advances in improving the quality of life and prolonging life for individuals with advanced neuromuscular disease. These include the use of physical medicine techniques to balance extremity muscle strength and improve range of motion and noninvasive techniques to provide inspiratory and expiratory muscle assistance to prolong life without resort to tracheostomy. Such advances help eliminate the "crisis" decision making about "going on a respirator" and sophisticated assistive equipment and robotic aids. Physicians and society in general use quality of life issues inappropriately derived by questioning physically able individuals to justify withholding or implementing life-sustaining therapeutic interventions for these individuals. Informed decisions about ethically and financially complex matters such as long-term ventilator use should be made by examining the life satisfaction of competent individuals who have already chosen these options. The great majority of severely disabled ventilator-assisted individuals with neuromuscular disease are satisfied with their lives despite the inability to achieve many of the "usual" goals associated with quality of life in the physically able population. Their principle life satisfaction derives from social relationships, the reorganization of goals and from their immediate environment. Although the Americans with Disabilities Act is seen as an important step to prevent discrimination against disabled individuals, it does little or nothing for the self-directed disabled individual who is not informed by his/her physicians regarding potentially vital therapeutic options nor does it help those who are warehoused in institutions because of lack of a national personal assistance services policy.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Regulation of quantal transmitter secretion by ATP and protein kinases at developing neuromuscular synapses.

    PubMed

    Fu, W M; Chen, Y H; Lee, K F; Liou, J C

    1997-04-01

    The effects of endogenously released ATP on the maturation of developing neuromuscular synapses were investigated in Xenopus nerve-muscle co-cultures. The potentiating action of ATP (1 mM) on spontaneous acetylcholine release was inhibited by P2-purinoceptor antagonists suramin (0.3 mM) and reactive blue 2 (RB-2, 3 microM) in day 1 cultures. Bath application of suramin (10 microM) or RB-2 in day 1 cultures and prolonged treatment for 2 days dramatically decreased the amplitude of both spontaneous synaptic currents (SSCs) and evoked synaptic currents (ESCs) in the same cultures on day 3. Chronic treatment with 8-cyclopentyltheophylline (4 microM) or 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX, 10 microM), P1-purinoceptor and glutamate receptor antagonists respectively, did not exert such an inhibitory effect. Chronic treatment with suramin or RB-2 for 2 days had no significant effect on the amplitude of either iontophoretic acetylcholine-induced whole-cell currents or single acetylcholine channel measurements in 3-day-old cultured myocytes. In addition, prolonged treatment for 2 days with various kinase inhibitors such as H-8 (10 microM), KN-62 (5 microM) and H-7 (10 microM) also decreased the amplitudes of both spontaneous and evoked synaptic currents in natural synapses, but not those of iontophoretic acetylcholine-induced currents. Furthermore, suramin and these protein kinase inhibitors also decreased the amplitude of spontaneous synaptic currents in manipulated synapses of 'vacated' nerve terminals. The results suggest that endogenously released ATP, acting in concert with various protein kinases, is involved in the maintenance and/or development of the quantum size of synaptic vesicles at embryonic neuromuscular synapses. PMID:9153574

  7. Effects of toxic extracts and purified borbotoxins from Prorocentrum borbonicum (Dinophyceae) on vertebrate neuromuscular junctions.

    PubMed

    Ten-Hage, Loïc; Robillot, Cédric; Turquet, Jean; Le Gall, Frédéric; Le Caer, Jean-Pierre; Bultel, Valérie; Guyot, Michèle; Molgó, Jordi

    2002-02-01

    Benthic dinoflagellates of the genus Prorocentrum are common in tropical and subtropical water and several species produce phycotoxins potentially involved in human toxic outbreaks. The toxic dinoflagellate Prorocentrum borbonicum collected at La Réunion Island (France) was cultured in laboratory. A crude extract of the organism displayed significant toxicity in mice characterized by progressive limb paralysis, severe dyspnea, and death, and the toxicity was retained, after partition, in the extract's butanol-soluble fraction (BSF). Electrophysiological experiments characterizing the fraction's effect on isolated vertebrate neuromuscular preparations revealed that it depolarizes the muscle membrane and reduces the driving force for endplate potentials (EPPs) evoked by nerve stimulation, blocking directly- and indirectly-elicited muscle twitches. The depolarization induced by P. borbonicum BSF was not due to Na(+) influx through voltage-dependent Na(+) channels, since tetrodotoxin neither prevented nor suppressed the depolarization. However, ouabain, a specific ligand of the Na/K ATPase, reduced the depolarization. These results suggest the presence of palytoxin-like compounds in the fraction. HPLC-MS and MS/MS analysis showed the presence of several toxins having identical UV absorbance, among which two new isomeric toxins, borbotoxin-A and -B, of molecular mass of 1037.6 Da were isolated. The purified borbotoxin-A, had no effect on the resting membrane potential of muscle fibers and did not affect directly-elicited muscle twitches. However, the toxin reduced nerve-evoked muscle twitches, in a dose-dependent manner, reduced EPPs' amplitudes and completely blocked miniature endplate potentials. These observations suggest that the main action of borbotoxin-A is to block post-synaptic nicotinic ACh receptors. PMID:11689235

  8. Reduced Expression of the Vesicular Acetylcholine Transporter and Neurotransmitter Content Affects Synaptic Vesicle Distribution and Shape in Mouse Neuromuscular Junction

    PubMed Central

    Rodrigues, Hermann A.; Fonseca, Matheus de C.; Camargo, Wallace L.; Lima, Patrícia M. A.; Martinelli, Patrícia M.; Naves, Lígia A.; Prado, Vânia F.; Prado, Marco A. M.; Guatimosim, Cristina

    2013-01-01

    In vertebrates, nerve muscle communication is mediated by the release of the neurotransmitter acetylcholine packed inside synaptic vesicles by a specific vesicular acetylcholine transporter (VAChT). Here we used a mouse model (VAChT KDHOM) with 70% reduction in the expression of VAChT to investigate the morphological and functional consequences of a decreased acetylcholine uptake and release in neuromuscular synapses. Upon hypertonic stimulation, VAChT KDHOM mice presented a reduction in the amplitude and frequency of miniature endplate potentials, FM 1–43 staining intensity, total number of synaptic vesicles and altered distribution of vesicles within the synaptic terminal. In contrast, under electrical stimulation or no stimulation, VAChT KDHOM neuromuscular junctions did not differ from WT on total number of vesicles but showed altered distribution. Additionally, motor nerve terminals in VAChT KDHOM exhibited small and flattened synaptic vesicles similar to that observed in WT mice treated with vesamicol that blocks acetylcholine uptake. Based on these results, we propose that decreased VAChT levels affect synaptic vesicle biogenesis and distribution whereas a lower ACh content affects vesicles shape. PMID:24260111

  9. Reduced expression of the vesicular acetylcholine transporter and neurotransmitter content affects synaptic vesicle distribution and shape in mouse neuromuscular junction.

    PubMed

    Rodrigues, Hermann A; Fonseca, Matheus de C; Camargo, Wallace L; Lima, Patrícia M A; Martinelli, Patrícia M; Naves, Lígia A; Prado, Vânia F; Prado, Marco A M; Guatimosim, Cristina

    2013-01-01

    In vertebrates, nerve muscle communication is mediated by the release of the neurotransmitter acetylcholine packed inside synaptic vesicles by a specific vesicular acetylcholine transporter (VAChT). Here we used a mouse model (VAChT KD(HOM)) with 70% reduction in the expression of VAChT to investigate the morphological and functional consequences of a decreased acetylcholine uptake and release in neuromuscular synapses. Upon hypertonic stimulation, VAChT KD(HOM) mice presented a reduction in the amplitude and frequency of miniature endplate potentials, FM 1-43 staining intensity, total number of synaptic vesicles and altered distribution of vesicles within the synaptic terminal. In contrast, under electrical stimulation or no stimulation, VAChT KD(HOM) neuromuscular junctions did not differ from WT on total number of vesicles but showed altered distribution. Additionally, motor nerve terminals in VAChT KD(HOM) exhibited small and flattened synaptic vesicles similar to that observed in WT mice treated with vesamicol that blocks acetylcholine uptake. Based on these results, we propose that decreased VAChT levels affect synaptic vesicle biogenesis and distribution whereas a lower ACh content affects vesicles shape. PMID:24260111

  10. Continuous neuromuscular blockade is associated with decreased mortality in post-cardiac arrest patients

    PubMed Central

    Salciccioli, Justin D.; Cocchi, Michael N.; Rittenberger, Jon C.; Peberdy, Mary Ann; Ornato, Joseph P.; Abella, Benjamin S.; Gaieski, David F.; Clore, John; Gautam, Shiva; Giberson, Tyler; Callaway, Clifton W.; Donnino, Michael W.

    2013-01-01

    Aim Neuromuscular blockade may improve outcome in patients with acute respiratory distress syndrome. In post-cardiac arrest patients receiving therapeutic hypothermia, neuromuscular blockade is often used to prevent shivering. Our objective was to determine whether neuromuscular blockade is associated with improved outcomes after out-of-hospital cardiac arrest. Methods A post-hoc analysis of a prospective observational study of comatose adult (> 18 years) out-of-hospital cardiac arrest at 4 tertiary cardiac arrest centers. The primary exposure of interest was neuromuscular blockade for 24 hours following return of spontaneous circulation and primary outcomes were in-hospital survival and neurologically intact survival. Secondary outcomes were evolution of oxygenation (PaO2:FiO2), and change in lactate. We tested the primary outcomes of in-hospital survival and neurologically intact survival with multivariable logistic regression. Secondary outcomes were tested with multivariable linear mixed-models. Results A total of 111 patients were analyzed. In patients with 24 hours of sustained neuromuscular blockade, the crude survival rate was 14/18 (78%) compared to 38/93 (41%) in patients without sustained neuromuscular blockade (p = 0.004). After multivariable adjustment, neuromuscular blockade was associated with survival (adjusted OR: 7.23, 95% CI: 1.56 –33.38). There was a trend toward improved functional outcome with neuromuscular blockade (50% vs. 28%; p = 0.07). Sustained neuromuscular blockade was associated with improved lactate clearance (adjusted p = 0.01). Conclusions We found that early neuromuscular blockade for a 24-hour period is associated with an increased probability of survival. Secondarily, we found that early, sustained neuromuscular blockade is associated with improved lactate clearance. PMID:23796602

  11. Presynaptic muscarinic and adenosine receptors are involved in 2 Hz-induced train-of-four fade caused by antinicotinic neuromuscular relaxants in the rat.

    PubMed

    Pereira, Mw; Bornia, Ecs; Correia-de-Sá, P; Alves-Do-Prado, W

    2011-11-01

    1. Train-of-four fade (TOF(fade) ) is a clinically useful parameter to monitor the degree of block of neuromuscular transmission in curarized patients. Experimentally, TOF(fade) has been attributed to the blockade of facilitatory nicotinic receptors on motor nerve terminals. There is less information regarding the involvement of coexistent presynaptic receptors (e.g. muscarinic M(1) and M(2) , adenosine A(1) and A(2A) ) in the TOF(fade) produced by antinicotinic agents. 2. In the present study, we evaluated the TOF(fade) caused by antinicotinic neuromuscular relaxants (hexamethonium, d-tubocurarine, vecuronium and rocuronium) as the ratio of the muscle tension produced in the rat diaphragm by the fourth to the first stimulus (T(4) /T(1) ) of a train-of-four stimuli delivered to the phrenic nerve trunk at a frequency of 2 Hz. 3. All antinicotinic agents, except hexamethonium, decreased the amplitude of muscle tension during the first stimulus. Hexamethonium, (5.47 mmol/L), d-tubocurarine- (1.1 μmol/L), vecuronium (4.7 μmol/L)- and rocuronium (9.8 μmol/L)-induced TOF(fade) was attenuated by 10 nmol/L pirenzepine (an M(1) receptor antagonist), 1 μmol/L methoctramine (an M(2) receptor antagonist) and 2.5 nmol/L 1,3-dipropyl-8-cyclopentylxanthine (an A(1) receptor antagonist). Blockade of the A(2A) receptor with 10 nmol/L ZM241385 partially reversed the TOF(fade) induced by d-tubocurarine, vecuronium and rocuronium, but not that caused by the 'pure' neuronal nicotinic receptor antagonist hexamethonium, unless one increased the concentration of ZM241385 to 50 nmol/L. 4. The data indicate that presynaptic M(1) , M(2) , A(1) and A(2A) receptors play a role in neuromuscular TOF(fade) caused by antinicotinic neuromuscular relaxants. Such interplay depends on adenosine tonus and on the affinity of neuromuscular blocking agents for neuronal versus muscular nicotinic receptors.

  12. Types of Heart Block

    MedlinePlus

    ... Block Explore Heart Block What Is... Electrical System & EKG Results Types Causes Who Is at Risk Signs & ... the P and the R waves on the EKG (electrocardiogram). First-degree heart block may not cause ...

  13. Use of Single Fiber Electromyographic Jitter to Detect Acute Changes in Neuromuscular Function in Young and Adult Rats

    EPA Science Inventory

    INTRODUCTION: Exposure to irreversible cholinesterase (ChE)-inhibiting compounds, such as organophosphates may produce neuromuscular dysfunction. However, less is known about changes in neuromuscular transmission after treatment with reversible ChE-inhibitors. These studies adapt...

  14. Neuromuscular responses to simulated brazilian jiu-jitsu fights.

    PubMed

    da Silva, Bruno Victor Corrêa; Ide, Bernardo Neme; de Moura Simim, Mário Antônio; Marocolo, Moacir; da Mota, Gustavo Ribeiro

    2014-12-01

    The aim of this study was to investigate the neuromuscular performance responses following successive Brazilian Jiu-Jitsu (BJJ) fights. Twenty-three BJJ athletes (age: 26.3 ± 6.3 years; body mass: 79.4 ± 9.7 kg; body height: 1.80 ± 0.1 m) undertook 3 simulated BJJ fights (10 min duration each separated by 15 min of rest). Neuromuscular performance was measured by the bench press throw (BPT) and vertical counter movement jump (VCMJ) tests, assessed before the 1st fight (Pre) and after the last one (Post). Blood lactate (LA) was measured at Pre, 1 min Post, and 15 min Post fights. Paired t-tests were employed in order to compare the BPT and VCMJ results. One-way ANOVA with Bonferroni post hoc tests were utilized to compare LA responses. The results revealed a significant (p < 0.05) increase in VCMJ performance (40.8 ± 5.5 cm Pre vs. 42.0 ± 5.8 cm Post), but no significant changes in the BPT (814 ± 167 W Pre vs. 835 ± 213 W Post) were observed. LA concentration increased significantly (p < 0.05) at Post, both in the 1st min (10.4 ± 2.7 mmol L-1) and the 15th min (6.4 ± 2.5 mmol L-1) of recovery. We concluded that successive simulated BJJ fights demanded considerable anaerobic contribution of ATP supply, reinforcing the high-intensity intermittent nature of the sport. Nevertheless, no negative impact on acute neuromuscular performance (power) was observed.

  15. Neuromuscular Responses to Simulated Brazilian Jiu-Jitsu Fights

    PubMed Central

    da Silva, Bruno Victor Corrêa; Ide, Bernardo Neme; de Moura Simim, Mário Antônio; Marocolo, Moacir; da Mota, Gustavo Ribeiro

    2014-01-01

    The aim of this study was to investigate the neuromuscular performance responses following successive Brazilian Jiu-Jitsu (BJJ) fights. Twenty-three BJJ athletes (age: 26.3 ± 6.3 years; body mass: 79.4 ± 9.7 kg; body height: 1.80 ± 0.1 m) undertook 3 simulated BJJ fights (10 min duration each separated by 15 min of rest). Neuromuscular performance was measured by the bench press throw (BPT) and vertical counter movement jump (VCMJ) tests, assessed before the 1st fight (Pre) and after the last one (Post). Blood lactate (LA) was measured at Pre, 1 min Post, and 15 min Post fights. Paired t-tests were employed in order to compare the BPT and VCMJ results. One-way ANOVA with Bonferroni post hoc tests were utilized to compare LA responses. The results revealed a significant (p < 0.05) increase in VCMJ performance (40.8 ± 5.5 cm Pre vs. 42.0 ± 5.8 cm Post), but no significant changes in the BPT (814 ± 167 W Pre vs. 835 ± 213 W Post) were observed. LA concentration increased significantly (p < 0.05) at Post, both in the 1st min (10.4 ± 2.7 mmol L-1) and the 15th min (6.4 ± 2.5 mmol L-1) of recovery. We concluded that successive simulated BJJ fights demanded considerable anaerobic contribution of ATP supply, reinforcing the high-intensity intermittent nature of the sport. Nevertheless, no negative impact on acute neuromuscular performance (power) was observed. PMID:25713685

  16. Mechanical insufflation/exsufflation improves vital capacity in neuromuscular disorders.

    PubMed

    Stehling, Florian; Bouikidis, Anastasios; Schara, Ulrike; Mellies, Uwe

    2015-02-01

    Inherited neuromuscular disorders inevitably result in severe lung volume restriction associated with high morbidity and mortality. The aim of this retrospective study was to evaluate the long-term effects of the regular use of mechanical insufflation/exsufflation on the course of the vital capacity. This retrospective data analysis included 21 patients (16.1 ± 6.5 years) with neuromuscular disorders and severe lung volume restriction using nocturnal noninvasive ventilation. The patients were advised to regularly use the mechanical insufflation/exsufflation twice a day for 10 minutes applying sets of three insufflation/exsufflation breath via face mask irrespective of respiratory tract infection. Data on the course of vital capacity were collected 2 years prior and 2 years after the introduction of regular use of mechanical insufflation/exsufflation. Before the introduction of mechanical insufflation/exsufflation vital capacity decreased from 0.71 ± 0.38 L to 0.50 ± 0.24 L in the last year and from 0.88 ± 0.45 L to 0.71 ± 0.38 L in the next to last year. In the first year, after regular use of mechanical insufflation/exsufflation vital capacity significantly increased by 28% (from 0.50 L to 0.64 L)-after the second year the vital capacity increase remained stable (0.64 vs. 0.65 L). These data suggest that the regular use of mechanical insufflation/exsufflation improves vital capacity in patients with neuromuscular disorders and severe lung volume restriction.

  17. Clinical use of creatine in neuromuscular and neurometabolic disorders.

    PubMed

    Tarnopolsky, Mark A

    2007-01-01

    Many of the neuromuscular (e.g., muscular dystrophy) and neurometabolic (e.g., mitochondrial cytopathies) disorders share similar final common pathways of cellular dysfunction that may be favorably influenced by creatine monohydrate (CrM) supplementation. Studies using the mdx model of Duchenne muscular dystrophy have found evidence of enhanced mitochondrial function, reduced intra-cellular calcium and improved performance with CrM supplementation. Clinical trials in patients with Duchenne and Becker's muscular dystrophy have shown improved function, fat-free mass, and some evidence of improved bone health with CrM supplementation. In contrast, the improvements in function in myotonic dystrophy and inherited neuropathies (e.g., Charcot-Marie-Tooth) have not been significant. Some studies in patients with mitochondrial cytopathies have shown improved muscle endurance and body composition, yet other studies did not find significant improvements in patients with mitochondrial cytopathy. Lower-dose CrM supplementation in patients with McArdle's disease (myophosphorylase deficiency) improved exercise capacity, yet higher doses actually showed some indication of worsened function. Based upon known cellular pathologies, there are potential benefits from CrM supplementation in patients with steroid myopathy, inflammatory myopathy, myoadenylate deaminase deficiency, and fatty acid oxidation defects. Larger randomized control trials (RCT) using homogeneous patient groups and objective and clinically relevant outcome variables are needed to determine whether creatine supplementation will be of therapeutic benefit to patients with neuromuscular or neurometabolic disorders. Given the relatively low prevalence of some of the neuromuscular and neurometabolic disorders, it will be necessary to use surrogate markers of potential clinical efficacy including markers of oxidative stress, cellular energy charge, and gene expression patterns. PMID:18652078

  18. Neuromuscular activity of Bothrops fonsecai snake venom in vertebrate preparations

    PubMed Central

    Fernandes, Carla T; Giaretta, Vânia MA; Prudêncio, Luiz S; Toledo, Edvana O; da Silva, Igor RF; Collaço, Rita CO; Barbosa, Ana M; Hyslop, Stephen; Rodrigues-Simioni, Léa; Cogo, José C

    2014-01-01

    The neuromuscular activity of venom from Bothrops fonsecai, a lancehead endemic to southeastern Brazil, was investigated. Chick biventer cervicis (CBC) and mouse phrenic nerve-diaphragm (PND) preparations were used for myographic recordings and mouse diaphragm muscle was used for membrane resting potential (RP) and miniature end-plate potential (MEPP) recordings. Creatine kinase release and muscle damage were also assessed. In CBC, venom (40, 80 and 160μg/ml) produced concentration- and time-dependent neuromuscular blockade (50% blockade in 85±9 min and 73±8 min with 80 and 160μg/ml, respectively) and attenuated the contractures to 110μM ACh (78–100% inhibition) and 40mM KCl (45–90% inhibition). The venom-induced decrease in twitch-tension in curarized, directly-stimulated preparations was similar to that in indirectly stimulated preparations. Venom (100 and 200μg/ml) also caused blockade in PND preparations (50% blockade in 94±13 min and 49±8 min with 100 and 200μg/ml, respectively) but did not alter the RP or MEPP amplitude. In CBC, venom caused creatine kinase release and myonecrosis. The venom-induced decrease in twitch-tension and in the contractures to ACh and K+ were abolished by preincubating venom with commercial antivenom. These findings indicate that Bothrops fonsecai venom interferes with neuromuscular transmission essentially through postsynaptic muscle damage that affects responses to ACh and KCl. These actions are effectively prevented by commercial antivenom. PMID:25028603

  19. Rab3-GEF Controls Active Zone Development at the Drosophila Neuromuscular Junction1,2,3

    PubMed Central

    Bae, Haneui; Chen, Shirui; Roche, John P.; Ai, Minrong; Wu, Chunlai

    2016-01-01

    Abstract Synaptic signaling involves the release of neurotransmitter from presynaptic active zones (AZs). Proteins that regulate vesicle exocytosis cluster at AZs, composing the cytomatrix at the active zone (CAZ). At the Drosophila neuromuscular junction (NMJ), the small GTPase Rab3 controls the distribution of CAZ proteins across release sites, thereby regulating the efficacy of individual AZs. Here we identify Rab3-GEF as a second protein that acts in conjunction with Rab3 to control AZ protein composition. At rab3-GEF mutant NMJs, Bruchpilot (Brp) and Ca2+ channels are enriched at a subset of AZs, leaving the remaining sites devoid of key CAZ components in a manner that is indistinguishable from rab3 mutant NMJs. As the Drosophila homologue of mammalian DENN/MADD and Caenorhabditis elegans AEX-3, Rab3-GEF is a guanine nucleotide exchange factor (GEF) for Rab3 that stimulates GDP to GTP exchange. Mechanistic studies reveal that although Rab3 and Rab3-GEF act within the same mechanism to control AZ development, Rab3-GEF is involved in multiple roles. We show that Rab3-GEF is required for transport of Rab3. However, the synaptic phenotype in the rab3-GEF mutant cannot be fully explained by defective transport and loss of GEF activity. A transgenically expressed GTP-locked variant of Rab3 accumulates at the NMJ at wild-type levels and fully rescues the rab3 mutant but is unable to rescue the rab3-GEF mutant. Our results suggest that although Rab3-GEF acts upstream of Rab3 to control Rab3 localization and likely GTP-binding, it also acts downstream to regulate CAZ development, potentially as a Rab3 effector at the synapse. PMID:27022630

  20. 78 FR 78515 - Removal of JADE Act Tags

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-26

    ... Office of Foreign Assets Control Removal of JADE Act Tags ACTION: Notice. SUMMARY: The Treasury... provisions of the Tom Lantos Block Burmese JADE (Junta's Anti-Democratic Efforts) Act of 2008 (``JADE Act''). DATES: As of August 7, 2013, the financial and blocking provisions of Section 5(b) of the JADE Act...

  1. Imaging Acute Neuromuscular Explants from Thy1 Mouse Lines.

    PubMed

    Marinković, Petar; Godinho, Leanne; Misgeld, Thomas

    2015-09-01

    Because core facilities that generate transgenic founder mice for a reasonable fee are now available at most major research institutions, generating new Thy1-XFP transgenic animals (in which XFP stands for any fluorescent protein) is an option even for relatively small laboratories. Here, we provide a protocol for screening offspring of Thy1 transgenic founders. Acute neuromuscular explants are obtained from 3-wk-old F1 mice that have been produced by crossing Thy1 transgenic founders and commercially obtained inbred mice. Thy1-driven expression is detected by fluorescence microscopy. PMID:26330628

  2. Assessing neuromuscular mechanisms in human-exoskeleton interaction.

    PubMed

    Sylla, N; Bonnet, V; Venture, G; Armande, N; Fraisse, P

    2014-01-01

    In this study, we propose to evaluate a 7 DOF exoskeleton in terms of motion control. Using criteria from the human motor control literature, inverse optimization was performed to assess an industrial screwing movement. The results of our study show that the hybrid composition of the free arm movement was accurately determined. At contrary, when wearing the exoskeleton, which produces an arbitrary determined torque compensation, the motion is different from the naturally adopted one. This study is part of the evaluation and comprehension of the complex neuromuscular mechanism resulting in wearing an exoskeleton several hours per day for industrial tasks assistance.

  3. To build a synapse: signaling pathways in neuromuscular junction assembly

    PubMed Central

    Wu, Haitao; Xiong, Wen C.; Mei, Lin

    2010-01-01

    Synapses, as fundamental units of the neural circuitry, enable complex behaviors. The neuromuscular junction (NMJ) is a synapse type that forms between motoneurons and skeletal muscle fibers and that exhibits a high degree of subcellular specialization. Aided by genetic techniques and suitable animal models, studies in the past decade have brought significant progress in identifying NMJ components and assembly mechanisms. This review highlights recent advances in the study of NMJ development, focusing on signaling pathways that are activated by diffusible cues, which shed light on synaptogenesis in the brain and contribute to a better understanding of muscular dystrophy. PMID:20215342

  4. Block ground interaction of rockfalls

    NASA Astrophysics Data System (ADS)

    Volkwein, Axel; Gerber, Werner; Kummer, Peter

    2016-04-01

    During a rockfall the interaction of the falling block with the ground is one of the most important factors that define the evolution of a rockfall trajectory. It steers the rebound, the rotational movement, possibly brake effects, friction losses and damping effects. Therefore, if most reliable rockfall /trajectory simulation software is sought a good understanding of the block ground interaction is necessary. Today's rockfall codes enable the simulation of a fully 3D modelled block within a full 3D surface . However, the details during the contact, i.e. the contact duration, the penetration depth or the dimension of the marks in the ground are usually not part of the simulation. Recent field tests with rocks between 20 and 80 kg have been conducted on a grassy slope in 2014 [1]. A special rockfall sensor [2] within the blocks measured the rotational velocity and the acting accelerations during the tests. External video records and a so-called LocalPositioningSystem deliver information on the travel velocity. With these data not only the flight phases of the trajectories but also the contacts with the ground can be analysed. During the single jumps of a block the flight time, jump length, the velocity, and the rotation are known. During the single impacts their duration and the acting accelerations are visible. Further, the changes of rotational and translational velocity influence the next jump of the block. The change of the rotational velocity over the whole trajectory nicely visualizes the different phases of a rockfall regarding general acceleration and deceleration in respect to the inclination and the topography of the field. References: [1] Volkwein A, Krummenacher B, Gerber W, Lardon J, Gees F, Brügger L, Ott T (2015) Repeated controlled rockfall trajectory testing. [Abstract] Geophys. Res. Abstr. 17: EGU2015-9779. [2] Volkwein A, Klette J (2014) Semi-Automatic Determination of Rockfall Trajectories. Sensors 14: 18187-18210.

  5. Does quadriceps neuromuscular activation capability explain mobility function among older men and women?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related impairment of neuromuscular activation has been shown to contribute to weakness in older adults. However, it is unclear to what extent impaired neuromuscular activation independently accounts for decline of mobility function. The hypothesis of this study is that capability to produce rap...

  6. Does neuromuscular activation capability explain mobility function among older men and women?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related impairment of neuromuscular activation has been shown to contribute to weakness in older adults. However, it is unclear to what extent impaired neuromuscular activation independently accounts for decline of mobility function. The hypothesis of this study is that capability to produce rap...

  7. Update on neuromuscular disorders in pediatric orthopaedics: Duchenne muscular dystrophy, myelomeningocele, and cerebral palsy.

    PubMed

    Chambers, Henry G

    2014-01-01

    The purpose of this seminar was to review a large range of lower extremity and neuromuscular disorders. Because of the diversity of the topics covered, including clubfoot and vertical talus treatment, management of Legg-Calve-Perthes disease, and limb lengthening in dwarfism, this review will focus on the neuromuscular subsection reviewing the current management of the muscular dystrophies, myelomeningocele, and cerebral palsy.

  8. Action of some bisquaternary derivatives of phthalic acids and related substances on neuromuscular transmission

    PubMed Central

    Danilov, A. F.; Kvitko, I. J.; Lavrentieva, V. V.; Michelson, M. J.; Porai-Koshits, B. A.; Rozhkova, E. K.; Shelkovnikov, S. A.

    1972-01-01

    1. All the bisquaternary derivatives of terephthalic acid with three methyl groups on each nitrogen atom (PK-107, PK-95, PK-97 and PK-126) were depolarizing neuromuscular blocking agents. The most active was the compound PK-97, in which the two quaternary groups are separated by sixteen atoms and are about 20 Å (2 nm) apart. Activity was reduced many fold either by decreasing the separation to twelve atoms or by increasing it to eighteen atoms. It was also reduced several hundred fold when one trimethylammonium group in PK-97 was replaced by a hydrogen atom (as in PK-119). 2. The presence and position of the ester groups in these compounds is important; depolarizing activity is in most cases greatest when the ester groups are the same distance from the quaternary nitrogen atoms as in acetylcholine, that is, in carbolonium, sebacoyldicholine and PK-154. The monoquaternary analogues of carbolonium and sebacoyldicholine are appreciably active, having between about one-tenth to one-fifth of the activity of their bisquaternary analogues. 3. The relationships between the structure and activity of these compounds are discussed, particular consideration being given to the structure of the chain separating the quaternary groups and the arrangement of acetylcholine receptors on cells and of esterbinding groups within these receptors. PMID:4339387

  9. [Range of neuromuscular involvement in 47 patients infected with the human immunodeficiency virus].

    PubMed

    Ghika-Schmid, F; Kuntzer, T; Chave, J P; Miklossy, J; Regli, F

    1994-05-14

    Over a 30 month period, 47 out of 749 patients infected with the human immunodeficiency virus had various neuromuscular symptoms. Based on clinical and electrophysiological data, 47% had distal symmetric polyneuropathy, 11% chronic inflammatory demyelinating polyneuropathy (CIDP), 8.5% toxic neuropathy related to 2-3-dideoxyinosine (DDI), 8.5% cranial neuropathy, 8.5% mononeuropathy multiplex or isolated focal neuropathy, 8.5% progressive lumbosacral polyradiculopathy, and 8.5% myopathy. Half of the patients exhibited previous or concomitant signs of central nervous system involvement and 18 patients died during the study period. CIDP and cranial neuropathies usually appeared early in the course of the disease and consequently showed neurological improvement. Nerve conduction studies of DDI related toxic neuropathies showed distal axono-myelinic sensitivo-motor neuropathy, differing from CIDP by the absence of a conduction block. Distal symmetric polyneuropathies, frequent in the advanced systemic illness, do not systematically require an extended workup, but more unusual peripheral neuropathies which might be treatable necessitate further investigations (electromyography, radiology, serological blood tests; protein chemistry and routine workup of the cerebrospinal fluid). For example, progressive lumbosacral polyradiculopathies responded to early treatment, with a better outcome in one case of herpetic origin than in another case due to cytomegalovirus infection. Our observations suggest that myopathies in HIV infected patients should first be tackled by temporary interruption of virostatic medication, followed by muscle biopsy if the symptoms persist. PMID:8209201

  10. Drosophila Syncrip modulates the expression of mRNAs encoding key synaptic proteins required for morphology at the neuromuscular junction

    PubMed Central

    McDermott, Suzanne M.; Yang, Lu; Halstead, James M.; Hamilton, Russell S.; Meignin, Carine

    2014-01-01

    Localized mRNA translation is thought to play a key role in synaptic plasticity, but the identity of the transcripts and the molecular mechanism underlying their function are still poorly understood. Here, we show that Syncrip, a regulator of localized translation in the Drosophila oocyte and a component of mammalian neuronal mRNA granules, is also expressed in the Drosophila larval neuromuscular junction, where it regulates synaptic growth. We use RNA-immunoprecipitation followed by high-throughput sequencing and qRT-PCR to show that Syncrip associates with a number of mRNAs encoding proteins with key synaptic functions, including msp-300, syd-1, neurexin-1, futsch, highwire, discs large, and α-spectrin. The protein levels of MSP-300, Discs large, and a number of others are significantly affected in syncrip null mutants. Furthermore, syncrip mutants show a reduction in MSP-300 protein levels and defects in muscle nuclear distribution characteristic of msp-300 mutants. Our results highlight a number of potential new players in localized translation during synaptic plasticity in the neuromuscular junction. We propose that Syncrip acts as a modulator of synaptic plasticity by regulating the translation of these key mRNAs encoding synaptic scaffolding proteins and other important components involved in synaptic growth and function. PMID:25171822

  11. [Nerve ultrasound is useful for the diagnosis of neuromuscular diseases].

    PubMed

    Noto, Yu-Ichi

    2013-01-01

    High-resolution ultrasound allowed for more detailed morphological assessment peripheral nerves and muscles. It is important to elucidate ultrasound features of peripheral nerves or muscles in various neuromuscular diseases because ultrasound is a widely used, non-invasive and easily accessible diagnostic tool. We attempted to demonstrate characteristic findings of nerve ultrasound in patients with Charcot-Marie-Tooth disease (CMT), Amyotrophic lateral sclerosis (ALS), and Cervical radiculopathy. In patients with CMT1A, cross sectional areas (CSAs) of all the nerves we examined were significantly larger than those in normal controls. Additionally, median nerve CSA had positive correlation with CMT neuropathy score, and negative correlation with nerve conduction velocity. In patients with ALS, increased CSA forearm/upper arm ratio of the median nerve was a characteristic finding to support the diagnosis. In patients with cervical radiculopathy, we could observe that decreased CSA and diameter of the nerve root corresponding to the findings of MRI and electromyography. These results demonstrate that the combination of electrophysiological study, diagnostic imaging, and nerve ultrasound could lead to accurate diagnosis of various neuromuscular diseases.

  12. Neuromuscular and endocrine control of an avian courtship behavior.

    PubMed

    Schlinger, B A; Schultz, J D; Hertel, F

    2001-09-01

    In many species of birds, males perform complex visual and acoustic courtship displays to attract and stimulate females. Some of these displays involve considerable use of the wings and legs, suggesting that they may be controlled by sexually dimorphic spinal motoneurons and their target muscles. Sex steroid hormones are known to organize and activate many sexually dimorphic phenotypes, so these neuromuscular systems may also be steroid sensitive. To test these ideas, we have begun studies of wild golden-collared manakins (Manacus vitellinus) in Central America. Males of this species establish a courtship arena in the forest, where they perform an elaborate dance that includes use of their wings to generate loud snapping sounds. Here we describe male golden-collared manakin courtship behavior, including the various "wingsnaps." We also review our studies, and those of others, showing sexually dimorphic properties of manakin wings, the wing musculature, and sex steroid accumulation in the spinal cord. These data suggest that manakins are useful models for evaluating steroid control of complex peripheral neuromuscular systems. PMID:11534992

  13. Musculoskeletal and neuromuscular interventions: a physical approach to cystic fibrosis.

    PubMed Central

    Massery, Mary

    2005-01-01

    Children with CF are living longer than ever before, and thus issues pertaining to quality of life rather than just longevity of life need to be addressed by the entire healthcare team. This article addressed the issues pertaining to the external support of the dysfunctional internal organs: the secondary musculoskeletal (postural) and neuromuscular control deficits that occur to the maturing child with CF. The research pointed towards starting PT interventions for these deficits during the pre-pubescent phase when postural deficits were just emerging, but a suggestion was also made to explore whether these deficits can be even more effectively monitored and treated at an earlier age. The dual relationship between the muscles used to meet the increased respiratory demands of CF and the normal postural demands of physical activities was described through a model based on a soda-pop can and pressure support. A pre-pubescent child with a typical progression of CF was presented as a case report to illustrate how a PT programme that was focused on postural deficits could be implemented and what type of outcomes might be possible. The child made significant changes within a relatively short time frame of 4 months, proposing that the musculoskeletal and neuromuscular systems may play a significant role in the medical and physical long-term outcomes of CF. For that reason, the physical as well as medical needs of the patient should be incorporated into a comprehensive multi-system approach to the disease across the lifespan. PMID:16025768

  14. Structural abnormalities at neuromuscular synapses lacking multiple syntrophin isoforms.

    PubMed

    Adams, Marvin E; Kramarcy, Neal; Fukuda, Taku; Engel, Andrew G; Sealock, Robert; Froehner, Stanley C

    2004-11-17

    The syntrophins are modular adapter proteins that function by recruiting signaling molecules to the cytoskeleton via their direct association with proteins of the dystrophin protein family. We investigated the physiological function of beta2-syntrophin by generating a line of mice lacking this syntrophin isoform. The beta2-syntrophin null mice show no overt phenotype, or muscular dystrophy, and form structurally normal neuromuscular junctions (NMJs). To determine whether physiological consequences caused by the lack of beta2-syntrophin were masked by compensation from the alpha-syntrophin isoform, we crossed these mice with our previously described alpha-syntrophin null mice to produce mice lacking both isoforms. The alpha/beta2-syntrophin null mice have NMJs that are structurally more aberrant than those lacking only alpha-syntrophin. The NMJs of the alpha/beta2-syntrophin null mice have fewer junctional folds than either parent strain, and the remaining folds are abnormally shaped with few openings to the synaptic space. The levels of acetylcholine receptors are reduced to 23% of wild type in mice lacking both syntrophin isoforms. Furthermore, the alpha/beta2-syntrophin null mice ran significantly shorter distances on voluntary exercise wheels despite having normal neuromuscular junction transmission as determined by micro-electrode recording of endplate potentials. We conclude that both alpha-syntrophin and beta2-syntrophin play distinct roles in forming and maintaining NMJ structure and that each syntrophin can partially compensate for the loss of the other.

  15. Sarcocystis fayeri in skeletal muscle of horses with neuromuscular disease.

    PubMed

    Aleman, Monica; Shapiro, Karen; Sisó, Silvia; Williams, Diane C; Rejmanek, Daniel; Aguilar, Beatriz; Conrad, Patricia A

    2016-01-01

    Recent reports of Sarcocystis fayeri-induced toxicity in people consuming horse meat warrant investigation on the prevalence and molecular characterization of Sarcocystis spp. infection in horses. Sarcocysts in skeletal muscle of horses have been commonly regarded as an incidental finding. In this study, we investigated the prevalence of sarcocysts in skeletal muscle of horses with neuromuscular disease. Our findings indicated that S. fayeri infection was common in young mature horses with neuromuscular disease and could be associated with myopathic and neurogenic processes. The number of infected muscles and number of sarcocysts per muscle were significantly higher in diseased than in control horses. S. fayeri was predominantly found in low oxidative highly glycolytic myofibers. This pathogen had a high glycolytic metabolism. Common clinical signs of disease included muscle atrophy, weakness with or without apparent muscle pain, gait deficits, and dysphagia in horses with involvement of the tongue and esophagus. Horses with myositis were lethargic, apparently painful, stiff, and reluctant to move. Similar to humans, sarcocystosis and cardiomyopathy can occur in horses. This study did not establish causality but supported a possible association (8.9% of cases) with disease. The assumption of Sarcocysts spp. being an incidental finding in every case might be inaccurate.

  16. Innervation and neuromuscular control in ageing skeletal muscle.

    PubMed

    Hepple, Russell T; Rice, Charles L

    2016-04-15

    Changes in the neuromuscular system affecting the ageing motor unit manifest structurally as a reduction in motor unit number secondary to motor neuron loss; fibre type grouping due to repeating cycles of denervation-reinnervation; and instability of the neuromuscular junction that may be due to either or both of a gradual perturbation in postsynaptic signalling mechanisms necessary for maintenance of the endplate acetylcholine receptor clusters or a sudden process involving motor neuron death or traumatic injury to the muscle fibre. Functionally, these changes manifest as a reduction in strength and coordination that precedes a loss in muscle mass and contributes to impairments in fatigue. Regular muscle activation in postural muscles or through habitual physical activity can attenuate some of these structural and functional changes up to a point along the ageing continuum. On the other hand, regular muscle activation in advanced age (>75 years) loses its efficacy, and at least in rodents may exacerbate age-related motor neuron death. Transgenic mouse studies aimed at identifying potential mechanisms of motor unit disruptions in ageing muscle are not conclusive due to many different mechanisms converging on similar motor unit alterations, many of which phenocopy ageing muscle. Longitudinal studies of ageing models and humans will help clarify the cause and effect relationships and thus, identify relevant therapeutic targets to better preserve muscle function across the lifespan. PMID:26437581

  17. Intestinal Neuromuscular Function after Preservation and Transplantation1

    PubMed Central

    Hamada, Nobuo; Hutson, William R.; Nakada, Koji; Ikoma, Akira; Suzuki, Tomomi; Zhu, Yue; Starzl, Thomas E.; Todo, Satoru

    2010-01-01

    While it is well known that prolonged preservation of the intestinal graft causes severe mucosal damage after transplantation, little is known about the effect on neuromuscular function. The entire small intestine of adult hound dogs was flushed and preserved with cold lactated Ringer’s solution and autotransplanted either immediately (n = 6) or after 24 hr (n = 6). Animals undergoing sham operation (n = 4) were used as a control. Fasting motility and the response of the intestinal smooth muscle and enteric nerves to bethanechol (100 μg/kg/0.5 hr, iv) and cisapride (0.5 mg/kg, iv) were determined by a multiple strain gauge method on Postoperative Days 2, 4, 7, 14, 21, and 28. Compared to the control, immediately transplanted grafts and those preserved for 24 hr developed delayed reappearance of migrating myoelectric complexes (MMC), hypercontractile activity, and reduced response to bethanechol and cisapride administration. Animals in the preservation group developed more abnormal fasting motility after transplantation, but responses to bethanechol and cisapride stimulation were not markedly different from those of the immediate group. The reappearance of MMC occurred 3 weeks postoperatively in the preservation group compared to 2 days in the immediate group. The results of our study indicate that intestinal dysmotility is augmented in prolonged-preservation grafts compared to those with brief preservation. The dysmotility was transient and normalized 3 to 4 weeks after surgery. Preservation and reperfusion injury to the neuromuscular system of intestinal grafts are reversible and are attenuated by simple hypothermia. PMID:8661243

  18. Proprioception and Neuromuscular Control of the Shoulder After Muscle Fatigue

    PubMed Central

    Myers, Joseph B.; Guskiewicz, Kevin M.; Schneider, Robert A.; Prentice, William E.

    1999-01-01

    Objective: To examine the effects of fatigue on proprioception and neuromuscular control of the shoulder. Design and Setting: Subjects were randomly assigned to either an experimental group or control group. Subjects were tested using either the active angle-reproduction or the single- arm dynamic stability test. The subjects were then fatigued using a dynamometer performing continuous, concentric rotation exercises of the shoulder. Once fatigued, the subjects were posttested using the same test. One week later, the subjects returned and were pretested, fatigued, and posttested using the other test. Subjects: Thirty-two college-age (18 to 25 years) subjects (16 males, 16 females) with no history of glenohumeral instability or upper extremity injury volunteered for this study. Measurements: Absolute angular error was measured using an electrogoniometer present within the isokinetic dynamometer, while sway velocity was measured using a force-plate system. Results: Repeated-measures analysis of variance revealed a significant difference between the pretest and posttest values for absolute angular error in the experimental group, whereas no significant difference was revealed between pretest and posttest sway velocity for either the control or experimental group. Conclusions: Fatigue of the internal and external rotators of the shoulder decreased proprioception of the shoulder, while having no significant effect on neuromuscular control. ImagesFigure 1.Figure 2.Figure 3. PMID:16558590

  19. Creative Construction: Unit Blocks.

    ERIC Educational Resources Information Center

    Texas Child Care, 1999

    1999-01-01

    Describes the use of unit blocks with young children in early childhood education (ECE) settings to expand all areas of the curriculum. Discusses the origin of blocks in ECE programs, presents developmental stages of block play, describes children's building styles, and makes recommendations for getting started in block play for children of…

  20. Train-of-four fade during neuromuscular blockade induced by tubocurarine, succinylcholine or alpha-bungarotoxin in the rat isolated hemidiaphragm.

    PubMed

    Cheah, L S; Gwee, M C

    1988-12-01

    1. Nerve-evoked maximal twitches (T1, T2, T3, T4) of the rat isolated hemidiaphragm to train-of-four (TOF) stimulation (2 Hz X 2 s) were recorded continuously in the absence or presence of tubocurarine (1.5 mumol/l), succinylcholine (40 mumol/l) or alpha-bungarotoxin (1 mumol/l). The T1 and T4 response-time profiles for the three drugs were analysed with respect to amplitude depression and the TOF ratio (T4/T1) during the development of and recovery from neuromuscular blockade. 2. Tubocurarine produced T1 block accompanied by intense TOF fade; for the same degree of T1 block, the TOF ratio was lower during the recovery from blockade after washing out tubocurarine from the bath than during the onset of blockade. There was also a correspondingly slower recovery of the TOF ratio from 90% T1 block to control levels when compared with the time for complete T1 recovery. Fade and twitch tension depression were shown clearly to be separate responses, each with its own response-time profile. Fade is therefore not simply a consequence of postjunctional cholinoceptor blockade. 3. Succinylcholine produced T1 block with only moderate TOF fade; similar recovery rates from 90% T1 block to control levels were obtained for T1 and the TOF ratio. 4. alpha-Bungarotoxin produced irreversible and complete neuromuscular blockade during which TOF fade was virtually absent. 5. The results obtained in this study closely resemble those from other similar studies in animals and in humans and clearly demonstrate that the rat isolated hemidiaphragm is a suitable in vitro model for time course studies on TOF fade.

  1. Variation in Dube3a expression affects neurotransmission at the Drosophila neuromuscular junction.

    PubMed

    Valdez, Colleen; Scroggs, Reese; Chassen, Rachel; Reiter, Lawrence T

    2015-01-01

    Changes in UBE3A expression levels in neurons can cause neurogenetic disorders ranging from Angelman syndrome (AS) (decreased levels) to autism (increased levels). Here we investigated the effects on neuronal function of varying UBE3A levels using the Drosophila neuromuscular junction as a model for both of these neurogenetic disorders. Stimulations that evoked excitatory junction potentials (EJPs) at 1 Hz intermittently failed to evoke EJPs at 15 Hz in a significantly higher proportion of Dube3a over-expressors using the pan neuronal GAL4 driver C155-GAL4 (C155-GAL4>UAS-Dube3a) relative to controls (C155>+ alone). However, in the Dube3a over-expressing larval neurons with no failures, there was no difference in EJP amplitude at the beginning of the train, or the rate of decrease in EJP amplitude over the course of the train compared to controls. In the absence of tetrodotoxin (TTX), spontaneous EJPs were observed in significantly more C155-GAL4>UAS-Dube3a larva compared to controls. In the presence of TTX, spontaneous and evoked EJPs were completely blocked and mEJP amplitude and frequency did not differ among genotypes. These data suggest that over-expression of wild type Dube3a, but not a ubiquitination defective Dube3a-C/A protein, compromises the ability of motor neuron axons to support closely spaced trains of action potentials, while at the same time increasing excitability. EJPs evoked at 15 Hz in the absence of Dube3a (Dube3a(15b) homozygous mutant larvae) decayed more rapidly over the course of 30 stimulations compared to w(1118) controls, and Dube3a(15b) larval muscles had significantly more negative resting membrane potentials (RMP). However, these results could not be recapitulated using RNAi knockdown of Dube3a in muscle or neurons alone, suggesting more global developmental defects contribute to this phenotype. These data suggest that reduced UBE3A expression levels may cause global changes that affect RMP and neurotransmitter release from

  2. Testing block subdivision algorithms on block designs

    NASA Astrophysics Data System (ADS)

    Wiseman, Natalie; Patterson, Zachary

    2016-01-01

    Integrated land use-transportation models predict future transportation demand taking into account how households and firms arrange themselves partly as a function of the transportation system. Recent integrated models require parcels as inputs and produce household and employment predictions at the parcel scale. Block subdivision algorithms automatically generate parcel patterns within blocks. Evaluating block subdivision algorithms is done by way of generating parcels and comparing them to those in a parcel database. Three block subdivision algorithms are evaluated on how closely they reproduce parcels of different block types found in a parcel database from Montreal, Canada. While the authors who developed each of the algorithms have evaluated them, they have used their own metrics and block types to evaluate their own algorithms. This makes it difficult to compare their strengths and weaknesses. The contribution of this paper is in resolving this difficulty with the aim of finding a better algorithm suited to subdividing each block type. The proposed hypothesis is that given the different approaches that block subdivision algorithms take, it's likely that different algorithms are better adapted to subdividing different block types. To test this, a standardized block type classification is used that consists of mutually exclusive and comprehensive categories. A statistical method is used for finding a better algorithm and the probability it will perform well for a given block type. Results suggest the oriented bounding box algorithm performs better for warped non-uniform sites, as well as gridiron and fragmented uniform sites. It also produces more similar parcel areas and widths. The Generalized Parcel Divider 1 algorithm performs better for gridiron non-uniform sites. The Straight Skeleton algorithm performs better for loop and lollipop networks as well as fragmented non-uniform and warped uniform sites. It also produces more similar parcel shapes and patterns.

  3. Neuromuscular synaptic transmission in aged ganglioside-deficient mice.

    PubMed

    Zitman, Femke M P; Todorov, Boyan; Verschuuren, Jan J; Jacobs, Bart C; Furukawa, Keiko; Furukawa, Koichi; Willison, Hugh J; Plomp, Jaap J

    2011-01-01

    Gangliosides are sialylated glycosphingolipids that are present in high density on neuronal membranes, especially at synapses, where they are assumed to play functional or modulating roles. Mice lacking GM2/GD2-synthase express only the simple gangliosides GD3 and GM3 and develop progressive motor behaviour deficits upon ageing, apparently due to failing complex ganglioside-dependent maintenance and/or repair processes or, alternatively, toxic GM3/GD3 accumulation. We investigated the function of neuromuscular junctions (NMJs) of aged (>9 month-old) GM2/GD2-synthase null-mutant mice, because synaptic dysfunction might develop with age and could potentially contribute to the late-onset motor phenotype. In addition, we studied NMJs of old mice lacking GD3-synthase (expressing only O- and a-series gangliosides), which do not show an overt neurological phenotype but may develop subclinical synaptic deficits. Detailed electrophysiological analyses showed subtle changes in presynaptic neurotransmitter release. Acetylcholine release at 40 Hz nerve stimulation at aged GM2/GD2-synthase null-mutant NMJs ran down slightly more pronounced than at wild-type NMJs, and spontaneous acetylcholine release rate at GD3-synthase null-mutant NMJs was somewhat higher than at wild-type, selectively at 25 °C bath temperature. Interestingly, we observed faster kinetics of postsynaptic electrophysiological responses at aged GD3-synthase null-mutant NMJs, not previously seen by us at NMJs of young GD3-synthase null-mutants or other types of (aged or young) ganglioside-deficient mice. These kinetic changes might reflect a change in postsynaptic acetylcholine receptor behaviour. Our data indicate that it is highly unlikely that transmission failure at NMJs contributes to the progressive motor defects of aged GM2/GD2-synthase null-mutants and that, despite some kinetic changes of synaptic signals, neuromuscular transmission remains successful in aged GD3-synthase null-mutant mice. Apparently

  4. Age‐related neuromuscular changes affecting human vastus lateralis

    PubMed Central

    Piasecki, M.; Ireland, A.; Stashuk, D.; Hamilton‐Wright, A.; Jones, D. A.

    2015-01-01

    Key points Skeletal muscle size and strength decline in older age.The vastus lateralis, a large thigh muscle, undergoes extensive neuromuscular remodelling in healthy ageing, as characterized by a loss of motor neurons, enlargement of surviving motor units and instability of neuromuscular junction transmission.The loss of motor axons and changes to motor unit potential transmission precede a clinically‐relevant loss of muscle mass and function. Abstract The anterior thigh muscles are particularly susceptible to muscle loss and weakness during ageing, although how this is associated with changes to neuromuscular structure and function in terms of motor unit (MU) number, size and MU potential (MUP) stability remains unclear. Intramuscular (I.M.) and surface electromyographic signals were recorded from the vastus lateralis (VL) during voluntary contractions held at 25% maximal knee extensor strength in 22 young (mean ± SD, 25.3 ± 4.8 years) and 20 physically active older men (71.4 ± 6.2 years). MUP size, firing rates, phases, turns and near fibre (NF) jiggle were determined and MU number estimates (MUNEs) were made by comparing average surface MUP with maximal electrically‐evoked compound muscle action potentials. Quadriceps cross‐sectional area was measured by magnetic resonance imaging. In total, 379 individual MUs were sampled in younger men and 346 in older men. Compared to the MU in younger participants, those in older participants had 8% lower firing rates and larger MUP size (+25%), as well as increased complexity, as indicated by phases (+13%), turns (+20%) and NF jiggle (+11%) (all P < 0.0005). The MUNE values (derived from the area of muscle in range of the surface‐electrode) in older participants were ∼70% of those in the young (P < 0.05). Taking into consideration the 30% smaller cross‐sectional area of the VL, the total number of MUs in the older muscles was between 50% and 60% lower compared to in young muscles (P < 0

  5. Neuromuscular action of Bothrops lanceolatus (Fer de lance) venom and a caseinolytic fraction.

    PubMed

    Lôbo de Araújo, Albetiza; Donato, José Luiz; Leite, Gildo Bernardo; Prado-Franceschi, Júlia; Fontana, Marcos Dias; Bon, Cassian; Rodrigues Simioni, Léa

    2002-09-01

    A protein capable of inducing neuromuscular blockade in avian preparations and of depolarizing mouse diaphragm muscle was isolated from Bothrops lanceolatus venom using gel filtration and ion-exchange chromatography. The purified protein was a single chain polypeptide with an estimated molecular mass of 27.5 kDa by SDS-PAGE and had caseinolytic activity (13.3 units/mg), but no phospholipase A(2). B.lanceolatus venom (50 micro g/ml) and the caseinolytic protein (20 micro g/ml) produced contracture and progressive irreversible blockade (50% in 25+/-5 min (SEM) and 45+/-15 min, respectively), in indirectly stimulated chick biventer cervicis preparations. The contractile responses to acetylcholine (ACh; 37 and 74 micro M, n=6) were inhibited by venom and the caseinolytic protein, whereas those to potassium (13.4mM, n=6) were not. Membrane resting potential measurements in mouse hemidiaphragm preparations showed that B.lanceolatus venom and the purified protein caused depolarization which was prevented by D-tubocurarine (14.6mM). The venom produced a slight increase in the amplitude and frequency of miniature end-plate potentials, but this effect was not seen with the purified fraction. These results suggest that the purified protein acts exclusively post-synaptically. PMID:12220713

  6. The Role of Musculoskeletal Dynamics and Neuromuscular Control in Stress Development in Bone

    NASA Technical Reports Server (NTRS)

    DeWoody, Yssa

    1996-01-01

    The role of forces produced by the musculotendon units in the stress development of the long bones during gait has not been fully analyzed. It is well known that the musculotendons act as actuators producing the joint torques which drive the body. Although the joint torques required to perform certain motor tasks can be recovered through a kinematic analysis, it remains a difficult problem to determine the actual forces produced by each muscle that resulted in these torques. As a consequence, few studies have focused on the role of individual muscles in the development of stress in the bone. This study takes a control theoretic approach to the problem. A seven-link, eight degrees of freedom model of the body is controlled by various muscle groups on each leg to simulate gait. The simulations incorporate Hill-type models of muscles with activation and contraction dynamics controlled through neural inputs. This direct approach allows one to know the exact muscle forces exerted by each musculotendon throughout the gait cycle as well the joint torques and reaction forces at the ankle and knee. Stress and strain computed by finite element analysis on skeletal members will be related to these derived loading conditions. Thus the role of musculoskeletal dynamics and neuromuscular control in the stress development of the tibia during gait can be analyzed.

  7. A compartmentalized microfluidic neuromuscular co-culture system reveals spatial aspects of GDNF functions

    PubMed Central

    Zahavi, Eitan Erez; Ionescu, Ariel; Gluska, Shani; Gradus, Tal; Ben-Yaakov, Keren; Perlson, Eran

    2015-01-01

    ABSTRACT Bidirectional molecular communication between the motoneuron and the muscle is vital for neuromuscular junction (NMJ) formation and maintenance. The molecular mechanisms underlying such communication are of keen interest and could provide new targets for intervention in motoneuron disease. Here, we developed a microfluidic platform with motoneuron cell bodies on one side and muscle cells on the other, connected by motor axons extending through microgrooves to form functional NMJs. Using this system, we were able to differentiate between the proximal and distal effects of oxidative stress and glial-derived neurotrophic factor (GDNF), demonstrating a dying-back degeneration and retrograde transmission of pro-survival signaling, respectively. Furthermore, we show that GDNF acts differently on motoneuron axons versus soma, promoting axonal growth and innervation only when applied locally to axons. Finally, we track for the first time the retrograde transport of secreted GDNF from muscle to neuron. Thus, our data suggests spatially distinct effects of GDNF – facilitating growth and muscle innervation at axon terminals and survival pathways in the soma. PMID:25632161

  8. Distinct Roles of Muscle and Motoneuron LRP4 in Neuromuscular Junction Formation

    PubMed Central

    Wu, Haitao; Lu, Yisheng; Shen, Chengyong; Patel, Neil; Gan, Lin; Xiong, Wen C.; Mei, Lin

    2012-01-01

    SUMMARY Neuromuscular junction (NMJ) formation requires precise interaction between motoneurons and muscle fibers. LRP4 is a receptor of agrin that is thought to act incis to stimulate MuSK in muscle fibers for postsynaptic differentiation. Here we dissected the roles of LRP4 in muscle fibers and motoneurons in NMJ formation by cell-specific mutation. Studies of muscle-specific mutants suggest that LRP4 is involved in deciding where to form AChR clusters in muscle fibers, postsynaptic differentiation, and axon terminal development. LRP4 in HEK293 cells increased synapsin or SV2 puncta in contacting axons of co-cultured neurons, suggesting a synaptogenic function. Analysis of LRP4 muscle and motoneuron double mutants and mechanistic studies suggest that NMJ formation may also be regulated by LRP4 in motoneurons, which could serve as agrin’s receptor in trans to induce AChR clusters. These observations uncovered distinct roles of LRP4 in motoneurons and muscles in NMJ development. PMID:22794264

  9. Distinct roles of muscle and motoneuron LRP4 in neuromuscular junction formation.

    PubMed

    Wu, Haitao; Lu, Yisheng; Shen, Chengyong; Patel, Neil; Gan, Lin; Xiong, Wen C; Mei, Lin

    2012-07-12

    Neuromuscular junction (NMJ) formation requires precise interaction between motoneurons and muscle fibers. LRP4 is a receptor of agrin that is thought to act in cis to stimulate MuSK in muscle fibers for postsynaptic differentiation. Here we dissected the roles of LRP4 in muscle fibers and motoneurons in NMJ formation by cell-specific mutation. Studies of muscle-specific mutants suggest that LRP4 is involved in deciding where to form AChR clusters in muscle fibers, postsynaptic differentiation, and axon terminal development. LRP4 in HEK293 cells increased synapsin or SV2 puncta in contacting axons of cocultured neurons, suggesting a synaptogenic function. Analysis of LRP4 muscle and motoneuron double mutants and mechanistic studies suggest that NMJ formation may also be regulated by LRP4 in motoneurons, which could serve as agrin's receptor in trans to induce AChR clusters. These observations uncovered distinct roles of LRP4 in motoneurons and muscles in NMJ development. PMID:22794264

  10. Nonmechanical Roles of Dystrophin and Associated Proteins in Exercise, Neuromuscular Junctions, and Brains

    PubMed Central

    Nichols, Bailey; Takeda, Shin’ichi; Yokota, Toshifumi

    2015-01-01

    Dystrophin-glycoprotein complex (DGC) is an important structural unit in skeletal muscle that connects the cytoskeleton (f-actin) of a muscle fiber to the extracellular matrix (ECM). Several muscular dystrophies, such as Duchenne muscular dystrophy, Becker muscular dystrophy, congenital muscular dystrophies (dystroglycanopathies), and limb-girdle muscular dystrophies (sarcoglycanopathies), are caused by mutations in the different DGC components. Although many early studies indicated DGC plays a crucial mechanical role in maintaining the structural integrity of skeletal muscle, recent studies identified novel roles of DGC. Beyond a mechanical role, these DGC members play important signaling roles and act as a scaffold for various signaling pathways. For example, neuronal nitric oxide synthase (nNOS), which is localized at the muscle membrane by DGC members (dystrophin and syntrophins), plays an important role in the regulation of the blood flow during exercise. DGC also plays important roles at the neuromuscular junction (NMJ) and in the brain. In this review, we will focus on recently identified roles of DGC particularly in exercise and the brain. PMID:26230713

  11. Building-block selectivity of polyketide synthases.

    PubMed

    Liou, Grace F; Khosla, Chaitan

    2003-04-01

    For the past decade, polyketide synthases have presented an exciting paradigm for the controlled manipulation of complex natural product structure. These multifunctional enzymes catalyze the biosynthesis of polyketide natural products by stepwise condensation and modification of metabolically derived building blocks. In particular, regioselective modification of polyketide structure is possible by alterations in either intracellular acyl-CoA pools or, more commonly, by manipulation of acyl transferases that act as the primary gatekeepers for building blocks.

  12. Structural Mechanisms of the Agrin-LRP4-MuSK Signaling Pathway in Neuromuscular Junction Differentiation

    PubMed Central

    Zong, Yinong; Jin, Rongsheng

    2015-01-01

    The neuromuscular junction (NMJ) is the most extensively studied model of neuronal synaptogenesis. Acetylcholine receptor (AChR) clustering on the postsynaptic membrane is a cardinal event in the differentiation of NMJs. AChR clustering and postsynaptic differentiation is orchestrated by sophisticated interactions among three proteins: the neuron-secreted proteoglycan agrin, the co-receptor LRP4, and the muscle-specific receptor tyrosine kinase MuSK. LRP4 and MuSK act as scaffolds for multiple binding partners, resulting in a complex and dynamic network of interacting proteins that is required for AChR clustering. In this review, we discuss the structural basis for NMJ postsynaptic differentiation mediated by the agrin-LRP4-MuSK signaling pathway. PMID:23178848

  13. Structural mechanisms of the agrin-LRP4-MuSK signaling pathway in neuromuscular junction differentiation.

    PubMed

    Zong, Yinong; Jin, Rongsheng

    2013-09-01

    The neuromuscular junction (NMJ) is the most extensively studied model of neuronal synaptogenesis. Acetylcholine receptor (AChR) clustering on the postsynaptic membrane is a cardinal event in the differentiation of NMJs. AChR clustering and postsynaptic differentiation is orchestrated by sophisticated interactions among three proteins: the neuron-secreted proteoglycan agrin, the co-receptor LRP4, and the muscle-specific receptor tyrosine kinase MuSK. LRP4 and MuSK act as scaffolds for multiple binding partners, resulting in a complex and dynamic network of interacting proteins that is required for AChR clustering. In this review, we discuss the structural basis for NMJ postsynaptic differentiation mediated by the agrin-LRP4-MuSK signaling pathway. PMID:23178848

  14. Neuromuscular medicine competency in physical medicine and rehabilitation residents: a method of development and assessment.

    PubMed

    Lin, Lei; Cuccurullo, Sara J; Innerfield, Caitlin E; Strax, Thomas E; Petagna, Anne

    2013-03-01

    This project endeavored to create an educational module including methodology to instruct physical medicine and rehabilitation residents in the evaluation and appropriate treatment of patients with neuromuscular disorders. It further sought to verify acquired competencies in neuromuscular rehabilitation through objective evaluation methodology. An American Association of Neuromuscular and Electrodiagnostic Medicine board-certified physician with 10 yrs of clinical experience in neuromuscular and general rehabilitation trained 19 residents using a standardized competency-based module. The residents were trained through clinical training, lectures, and review of self-assessment examination concepts from the American Academy of Physical Medicine & Rehabilitation syllabus provided in the Archives of Physical Medicine and Rehabilitation. After delivery of the educational module, knowledge acquisition and skill proficiency were measured in (1) completion of neuromuscular history and physical examination satisfactorily, (2) diagnosis and ability to design a patient care management plan via chart stimulated recall examinations, (3) physician-patient interaction via patient surveys, (4) physician-staff interaction via 360-degree global ratings, and (5) ability to write a comprehensive patient care report and to document a patient care management plan in accordance with Medicare guidelines via written patient reports. Assessment tools developed for this program address the basic competencies outlined by the Accreditation Council for Graduate Medical Education. To test the success of the standardized educational module, data were collected on an ongoing basis. The objective measures compared resident self-assessment examination scores in neuromuscular rehabilitation before and after the institution of the comprehensive neuromuscular competency module in the residency program. Nineteen (100%) of 19 residents successfully demonstrated proficiency in every segment of the

  15. Neuromuscular medicine competency in physical medicine and rehabilitation residents: a method of development and assessment.

    PubMed

    Lin, Lei; Cuccurullo, Sara J; Innerfield, Caitlin E; Strax, Thomas E; Petagna, Anne

    2013-03-01

    This project endeavored to create an educational module including methodology to instruct physical medicine and rehabilitation residents in the evaluation and appropriate treatment of patients with neuromuscular disorders. It further sought to verify acquired competencies in neuromuscular rehabilitation through objective evaluation methodology. An American Association of Neuromuscular and Electrodiagnostic Medicine board-certified physician with 10 yrs of clinical experience in neuromuscular and general rehabilitation trained 19 residents using a standardized competency-based module. The residents were trained through clinical training, lectures, and review of self-assessment examination concepts from the American Academy of Physical Medicine & Rehabilitation syllabus provided in the Archives of Physical Medicine and Rehabilitation. After delivery of the educational module, knowledge acquisition and skill proficiency were measured in (1) completion of neuromuscular history and physical examination satisfactorily, (2) diagnosis and ability to design a patient care management plan via chart stimulated recall examinations, (3) physician-patient interaction via patient surveys, (4) physician-staff interaction via 360-degree global ratings, and (5) ability to write a comprehensive patient care report and to document a patient care management plan in accordance with Medicare guidelines via written patient reports. Assessment tools developed for this program address the basic competencies outlined by the Accreditation Council for Graduate Medical Education. To test the success of the standardized educational module, data were collected on an ongoing basis. The objective measures compared resident self-assessment examination scores in neuromuscular rehabilitation before and after the institution of the comprehensive neuromuscular competency module in the residency program. Nineteen (100%) of 19 residents successfully demonstrated proficiency in every segment of the

  16. Diverticular Disease of the Colon: Neuromuscular Function Abnormalities.

    PubMed

    Bassotti, Gabrio; Villanacci, Vincenzo; Bernardini, Nunzia; Dore, Maria P

    2016-10-01

    Colonic diverticular disease is a frequent finding in daily clinical practice. However, its pathophysiological mechanisms are largely unknown. This condition is likely the result of several concomitant factors occurring together to cause anatomic and functional abnormalities, leading as a result to the outpouching of the colonic mucosa. A pivotal role seems to be played by an abnormal colonic neuromuscular function, as shown repeatedly in these patients, and by an altered visceral perception. There is recent evidence that these abnormalities might be related to the derangement of the enteric innervation, to an abnormal distribution of mucosal neuropeptides, and to low-grade mucosal inflammation. The latter might be responsible for the development of visceral hypersensitivity, often causing abdominal pain in a subset of these patients. PMID:27622368

  17. Isozyme patterns and protein profiles in neuromuscular disorders.

    PubMed

    Edwards, Y H; Tipler, T D; Morgan-Hughes, J A; Neerunjun, J S; Hopkinson, D A

    1982-06-01

    The isozyme patterns of six different enzymes and the polypeptide profiles of soluble proteins have been examined in muscle biopsy specimens from 74 patients with a wide variety of neuromuscular disorders. About half of the samples showed unusual features in at least one, and often several, of the enzymes and proteins tested. The extent of the biochemical abnormalities was roughly proportional to the severity of the disorders. In all cases the unusual isozymes and polypeptide profiles seemed to reflect a reversion to the fetal pattern of gene expression. However, this change appeared to occur in extant muscle and was not dependent on the appearance of new muscle fibres. Among the enzymes, phosphoglycerate mutase followed by creatine kinase appeared to be the most sensitive index of muscle disorder. The extent of the change in the muscle creatine kinase isozyme pattern was not correlated with the levels of serum creatine kinase activity.

  18. Isozyme patterns and protein profiles in neuromuscular disorders.

    PubMed Central

    Edwards, Y H; Tipler, T D; Morgan-Hughes, J A; Neerunjun, J S; Hopkinson, D A

    1982-01-01

    The isozyme patterns of six different enzymes and the polypeptide profiles of soluble proteins have been examined in muscle biopsy specimens from 74 patients with a wide variety of neuromuscular disorders. About half of the samples showed unusual features in at least one, and often several, of the enzymes and proteins tested. The extent of the biochemical abnormalities was roughly proportional to the severity of the disorders. In all cases the unusual isozymes and polypeptide profiles seemed to reflect a reversion to the fetal pattern of gene expression. However, this change appeared to occur in extant muscle and was not dependent on the appearance of new muscle fibres. Among the enzymes, phosphoglycerate mutase followed by creatine kinase appeared to be the most sensitive index of muscle disorder. The extent of the change in the muscle creatine kinase isozyme pattern was not correlated with the levels of serum creatine kinase activity. Images PMID:6286971

  19. Presynaptic elements involved in the maintenance of the neuromuscular junction

    NASA Technical Reports Server (NTRS)

    Burrows, G. H.

    1984-01-01

    Alterations in the neuromuscular junction were observed in rats preceding loss of muscle mass. In view of the possibility that these alterations involve changes in the secretion of myotrophic agents by presynaptic motor neurons, an investigation was undertaken to characterize a neuronall factor which is thought to be involved in the initiation and maintenance of cholinergic synapses. This factor, which is secreted into the incubation medium by NG108-15 neuroblastoma x glioma hybrid cells, induces the aggregation of nicotinic acetylcholine receptors on primary cultures of rat hindlimb myotubes. Previous attempts to purify this factor failed. Extensive washing of the NG108-15 cells with hepes-buffered salt solution followed by short (4 hour) collection times resulted in the collection of incubation medium containing maximal aggregation activity with as little as 5 ug secreted protein per ml of fresh medium. A three-fold increase in specific activity was obtained after anion exchange chromatography.

  20. A novel synaptic plasticity rule explains homeostasis of neuromuscular transmission

    PubMed Central

    Ouanounou, Gilles; Baux, Gérard; Bal, Thierry

    2016-01-01

    Excitability differs among muscle fibers and undergoes continuous changes during development and growth, yet the neuromuscular synapse maintains a remarkable fidelity of execution. Here we show in two evolutionarily distant vertebrates (Xenopus laevis cell culture and mouse nerve-muscle ex-vivo) that the skeletal muscle cell constantly senses, through two identified calcium signals, synaptic events and their efficacy in eliciting spikes. These sensors trigger retrograde signal(s) that control presynaptic neurotransmitter release, resulting in synaptic potentiation or depression. In the absence of spikes, synaptic events trigger potentiation. Once the synapse is sufficiently strong to initiate spiking, the occurrence of these spikes activates a negative retrograde feedback. These opposing signals dynamically balance the synapse in order to continuously adjust neurotransmitter release to a level matching current muscle cell excitability. DOI: http://dx.doi.org/10.7554/eLife.12190.001 PMID:27138195

  1. Systemic inflammatory response and neuromuscular involvement in amyotrophic lateral sclerosis

    PubMed Central

    Lu, Ching-Hua; Allen, Kezia; Oei, Felicia; Leoni, Emanuela; Kuhle, Jens; Tree, Timothy; Fratta, Pietro; Sharma, Nikhil; Sidle, Katie; Howard, Robin; Orrell, Richard; Fish, Mark; Greensmith, Linda; Pearce, Neil; Gallo, Valentina

    2016-01-01

    Objective: To evaluate the combined blood expression of neuromuscular and inflammatory biomarkers as predictors of disease progression and prognosis in amyotrophic lateral sclerosis (ALS). Methods: Logistic regression adjusted for markers of the systemic inflammatory state and principal component analysis were carried out on plasma levels of creatine kinase (CK), ferritin, and 11 cytokines measured in 95 patients with ALS and 88 healthy controls. Levels of circulating biomarkers were used to study survival by Cox regression analysis and correlated with disease progression and neurofilament light chain (NfL) levels available from a previous study. Cytokines expression was also tested in blood samples longitudinally collected for up to 4 years from 59 patients with ALS. Results: Significantly higher levels of CK, ferritin, tumor necrosis factor (TNF)–α, and interleukin (IL)–1β, IL-2, IL-8, IL-12p70, IL-4, IL-5, IL-10, and IL-13 and lower levels of interferon (IFN)–γ were found in plasma samples from patients with ALS compared to controls. IL-6, TNF-α, and IFN-γ were the most highly regulated markers when all explanatory variables were jointly analyzed. High ferritin and IL-2 levels were predictors of poor survival. IL-5 levels were positively correlated with CK, as was TNF-α with NfL. IL-6 was strongly associated with CRP levels and was the only marker showing increasing expression towards end-stage disease in the longitudinal analysis. Conclusions: Neuromuscular pathology in ALS involves the systemic regulation of inflammatory markers mostly active on T-cell immune responses. Disease stratification based on the prognostic value of circulating inflammatory markers could improve clinical trials design in ALS. PMID:27308305

  2. Combined application of neuromuscular electrical stimulation and voluntary muscular contractions.

    PubMed

    Paillard, Thierry

    2008-01-01

    Electromyostimulation (EMS) and voluntary muscle contraction (VC) constitute different modes of muscle activation and induce different acute physiological effects on the neuromuscular system. Long-term application of each mode of muscle activation can produce different muscle adaptations. It seems theoretically possible to completely or partially cumulate the muscle adaptations induced by each mode of muscle activation applied separately. This work consisted of examining the literature concerning the muscle adaptations induced by long-term application of the combined technique (CT) [i.e. EMS is combined with VC - non-simultaneously] compared with VC and/or EMS alone in healthy subjects and/or athletes and in post-operative knee-injured subjects. In general, CT induced greater muscular adaptations than VC whether in sports training or rehabilitation. This efficiency would be due to the fact that CT can facilitate cumulative effects of training completely or partially induced by VC and EMS practiced alone. CT also provides a greater improvement of the performance of complex dynamic movements than VC. However, EMS cannot improve coordination between different agonistic and antagonistic muscles and thus does not facilitate learning the specific coordination of complex movements. Hence, EMS should be combined with specific sport training to generate neuromuscular adaptations, but also allow the adjustment of motor control during a voluntary movement. Likewise, in a therapeutic context, CT was particularly efficient to accelerate recovery of muscle contractility during a rehabilitation programme. Strength loss and atrophy inherent in a traumatism and/or a surgical operation would be more efficiently compensated with CT than with VC. Furthermore, CT also restored more functional abilities than VC. Finally, in a rehabilitation context, EMS is complementary to voluntary exercise because in the early phase of rehabilitation it elicits a strength increase, which is necessary

  3. Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome

    PubMed Central

    Rowe, Peter C.; Fontaine, Kevin R.; Lauver, Megan; Jasion, Samantha E.; Marden, Colleen L.; Moni, Malini; Thompson, Carol B.; Violand, Richard L.

    2016-01-01

    Chronic fatigue syndrome (CFS) is a complex, multisystem disorder that can be disabling. CFS symptoms can be provoked by increased physical or cognitive activity, and by orthostatic stress. In preliminary work, we noted that CFS symptoms also could be provoked by application of longitudinal neural and soft tissue strain to the limbs and spine of affected individuals. In this study we measured the responses to a straight leg raise neuromuscular strain maneuver in individuals with CFS and healthy controls. We randomly assigned 60 individuals with CFS and 20 healthy controls to either a 15 minute period of passive supine straight leg raise (true neuromuscular strain) or a sham straight leg raise. The primary outcome measure was the symptom intensity difference between the scores during and 24 hours after the study maneuver compared to baseline. Fatigue, body pain, lightheadedness, concentration difficulties, and headache scores were measured individually on a 0–10 scale, and summed to create a composite symptom score. Compared to individuals with CFS in the sham strain group, those with CFS in the true strain group reported significantly increased body pain (P = 0.04) and concentration difficulties (P = 0.02) as well as increased composite symptom scores (all P = 0.03) during the maneuver. After 24 hours, the symptom intensity differences were significantly greater for the CFS true strain group for the individual symptom of lightheadedness (P = 0.001) and for the composite symptom score (P = 0.005). During and 24 hours after the exposure to the true strain maneuver, those with CFS had significantly higher individual and composite symptom intensity changes compared to the healthy controls. We conclude that a longitudinal strain applied to the nerves and soft tissues of the lower limb is capable of increasing symptom intensity in individuals with CFS for up to 24 hours. These findings support our preliminary observations that increased mechanical sensitivity may be a

  4. Effects of neuromuscular lags on controlling contact transitions

    PubMed Central

    Venkadesan, Madhusudhan; Valero-Cuevas, Francisco J.

    2009-01-01

    We present a numerical exploration of contact transitions with the fingertip. When picking up objects our fingertips must make contact at specific locations, and—upon contact—maintain posture while producing well-directed force vectors. However, the joint torques for moving the fingertip towards a surface (τm) are different from those for producing static force vectors (τf). We previously described the neural control of such abrupt transitions in humans, and found that unavoidable errors arise because sensorimotor time delays and lags prevent an instantaneous switch between different torques. Here, we use numerical optimization on a finger model to reveal physical bounds for controlling such rapid contact transitions. Resembling human data, it is necessary to anticipatorily switch joint torques to τf at about 30 ms before contact to minimize the initial misdirection of the fingertip force vector. This anticipatory strategy arises in our deterministic model from neuromuscular lags, and not from optimizing for robustness to noise/uncertainties. Importantly, the optimal solution also leads to a trade-off between the speed of force magnitude increase versus the accuracy of initial force direction. This is an alternative to prevailing theories that propose multiplicative noise in muscles as the driver of speed–accuracy trade-offs. We instead find that the speed–accuracy trade-off arises solely from neuromuscular lags. Finally, because our model intentionally uses idealized assumptions, its agreement with human data suggests that the biological system is controlled in a way that approaches the physical boundaries of performance. PMID:19218157

  5. Effects of neuromuscular lags on controlling contact transitions.

    PubMed

    Venkadesan, Madhusudhan; Valero-Cuevas, Francisco J

    2009-03-28

    We present a numerical exploration of contact transitions with the fingertip. When picking up objects our fingertips must make contact at specific locations, and-upon contact-maintain posture while producing well-directed force vectors. However, the joint torques for moving the fingertip towards a surface (tau(m)) are different from those for producing static force vectors (tau(f)). We previously described the neural control of such abrupt transitions in humans, and found that unavoidable errors arise because sensorimotor time delays and lags prevent an instantaneous switch between different torques. Here, we use numerical optimization on a finger model to reveal physical bounds for controlling such rapid contact transitions. Resembling human data, it is necessary to anticipatorily switch joint torques to tau(f )at about 30 ms before contact to minimize the initial misdirection of the fingertip force vector. This anticipatory strategy arises in our deterministic model from neuromuscular lags, and not from optimizing for robustness to noise/uncertainties. Importantly, the optimal solution also leads to a trade-off between the speed of force magnitude increase versus the accuracy of initial force direction. This is an alternative to prevailing theories that propose multiplicative noise in muscles as the driver of speed-accuracy trade-offs. We instead find that the speed-accuracy trade-off arises solely from neuromuscular lags. Finally, because our model intentionally uses idealized assumptions, its agreement with human data suggests that the biological system is controlled in a way that approaches the physical boundaries of performance.

  6. THREE-DIMENSIONAL ULTRASTRUCTURE OF THE CRAYFISH NEUROMUSCULAR APPARATUS

    PubMed Central

    Jahromi, S. S.; Atwood, H. L.

    1974-01-01

    The synapse-bearing nerve terminals of the opener muscle of the crayfish Procambarus were reconstructed using electron micrographs of regions which had been serially sectioned. The branching patterns of the terminals of excitatory and inhibitory axons and the locations and sizes of neuromuscular and axo-axonal synapses were studied. Excitatory and inhibitory synapses could be distinguished not only on the basis of differences in synaptic vesicles, but also by a difference in density of pre- and postsynaptic membranes. Synapses of both axons usually had one or more sharply localized presynaptic "dense bodies" around which synaptic vesicles appeared to cluster. Some synapses did not have the dense bodies. These structures may be involved in the physiological activity of the synapse. Excitatory axon terminals had more synapses, and a larger percentage of terminal surface area devoted to synaptic contacts, than inhibitory axon terminals. However, the largest synapses of the inhibitory axon exceeded in surface area those of the excitatory axon. Both axons had many side branches coming from the main terminal; often, the side branches were joined to the main terminal by narrow necks. A greater percentage of surface area was devoted to synapses in side branches than in the main terminal. Only a small fraction of total surface area was devoted to axo-axonal synapses, but these were often located at narrow necks or constrictions of the excitatory axon. This arrangement would result in effective blockage of spike invasion of regions of the terminal distal to the synapse, and would allow relatively few synapses to exert a powerful effect on transmitter release from the excitatory axon. A hypothesis to account for the development of the neuromuscular apparatus is presented, in which it is suggested that production of new synapses is more important than enlargement of old ones as a mechanism for allowing the axon to adjust transmitter output to the functional needs of the muscle

  7. Neuromuscular adaptations and correlates of knee functionality following ACL reconstruction.

    PubMed

    Bryant, Adam L; Kelly, Jason; Hohmann, Erik

    2008-01-01

    The objective of this research was to examine the dynamic restraint mechanism by establishing the neuromuscular characteristics of lower extremity muscles in anterior cruciate ligament reconstruction (ACLR) subjects. This study also investigated neuromuscular variables that relate to post-ACLR functional outcome. Thirteen patients having undergone ACLR using the bone patella tendon bone graft at least 6 months prior participated in this study. Knee functionality (0- to 100-point scale) was rated using the Cincinnati Knee Rating System. The median frequency of the electromyographic (EMG) recordings from the vastus medialis (VM) and vastus lateralis (VL) muscles together with the isokinetic quadriceps torque generated in 10 degrees intervals between 80 degrees and 10 degrees knee flexion was determined for the noninvolved and involved limbs. Lower limb musculotendinous stiffness was also assessed for the noninvolved and involved limbs. Limb symmetry indexes were calculated for each of the physiological measures. Compared to the noninvolved limb, the median frequency of the EMG from the involved limb VM and VL muscles was significantly lower as was the quadriceps torque generated at the seven knee flexion intervals. In contrast, musculotendinous stiffness was significantly higher in the involved lower limb compared to the noninvolved limb. Significant, moderate correlations were identified between knee functionality and symmetry indexes for all variables except for the isokinetic quadriceps torque produced between 80 degrees -70 degrees and 20 degrees -10 degrees knee flexion. More functional ACLR subjects demonstrated enhanced motor unit recruitment reflective of less quadriceps muscle fiber atrophy together with increased quadriceps strength and musculotendinous stiffness of the lower limb musculature.

  8. Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome.

    PubMed

    Rowe, Peter C; Fontaine, Kevin R; Lauver, Megan; Jasion, Samantha E; Marden, Colleen L; Moni, Malini; Thompson, Carol B; Violand, Richard L

    2016-01-01

    Chronic fatigue syndrome (CFS) is a complex, multisystem disorder that can be disabling. CFS symptoms can be provoked by increased physical or cognitive activity, and by orthostatic stress. In preliminary work, we noted that CFS symptoms also could be provoked by application of longitudinal neural and soft tissue strain to the limbs and spine of affected individuals. In this study we measured the responses to a straight leg raise neuromuscular strain maneuver in individuals with CFS and healthy controls. We randomly assigned 60 individuals with CFS and 20 healthy controls to either a 15 minute period of passive supine straight leg raise (true neuromuscular strain) or a sham straight leg raise. The primary outcome measure was the symptom intensity difference between the scores during and 24 hours after the study maneuver compared to baseline. Fatigue, body pain, lightheadedness, concentration difficulties, and headache scores were measured individually on a 0-10 scale, and summed to create a composite symptom score. Compared to individuals with CFS in the sham strain group, those with CFS in the true strain group reported significantly increased body pain (P = 0.04) and concentration difficulties (P = 0.02) as well as increased composite symptom scores (all P = 0.03) during the maneuver. After 24 hours, the symptom intensity differences were significantly greater for the CFS true strain group for the individual symptom of lightheadedness (P = 0.001) and for the composite symptom score (P = 0.005). During and 24 hours after the exposure to the true strain maneuver, those with CFS had significantly higher individual and composite symptom intensity changes compared to the healthy controls. We conclude that a longitudinal strain applied to the nerves and soft tissues of the lower limb is capable of increasing symptom intensity in individuals with CFS for up to 24 hours. These findings support our preliminary observations that increased mechanical sensitivity may be a

  9. Learning with Large Blocks.

    ERIC Educational Resources Information Center

    Cartwright, Sally

    1990-01-01

    Discusses how large hollow blocks can meet many preschool children's learning needs through creative dramatic play, and also gives some guidelines on how these blocks can be constructed by parents and teachers. (BB)

  10. Block That Pain!

    MedlinePlus

    ... combination produces a unique effect, blocking pain-sensing neurons without impairing signals from other cells. In contrast, ... surgical procedures block activity in all types of neurons. This can cause numbness, paralysis, and other nervous ...

  11. Inhibition of neuromuscular transmission in isolated mouse phrenic nerve-diaphragm by the enterotoxin of Clostridium perfringens type A.

    PubMed

    Sugimoto, N; Miyamoto, A; Horiguchi, Y; Okabe, T; Matsuda, M

    1992-08-01

    The enterotoxin of Clostridium perfringens type A, a channel forming protein toxin, inhibited neuromuscular transmission under conditions of low calcium. Twitch tension of isolated phrenic nerve-diaphragm preparations elicited by electrical stimulations to the phrenic nerve was recorded isometrically, and the preparations were exposed to the purified enterotoxin. In Krebs solution containing 0.5 mM calcium, the enterotoxin (20 micrograms/ml) reduced within 10 min the amplitude of the twitch tension to 34 +/- 7% (mean +/- S.D., n = 11) of that recorded before the treatment. The effects of the enterotoxin on the twitch tension were irreversible and proceeded independently of stimulation. The reduction of the twitch tension by the enterotoxin was apparent in Krebs solution containing less than 0.6 mM calcium and the degree of reduction was inversely related to the concentration of calcium. The reduction of the twitch tension by the enterotoxin was also dependent on temperature and concentration of the toxin. At temperatures below 20 degrees C, no obvious reduction of twitch tension was observed with 20 micrograms/ml of the enterotoxin. Enterotoxin at a concentration of 0.4 micrograms/ml caused 16 +/- 2% (mean +/- S.D., n = 4) reduction of twitch tension, and the degree of the reduction in twitch tension increased with toxin concentration, reaching a plateau of 65 +/- 4% (mean +/- S.D., n = 7) at 6.5 micrograms/ml of the enterotoxin. The effects of the enterotoxin were antagonized by 2 microM physostigmine. Unlike curare, pretreatment of the preparation with enterotoxin did not antagonize the neuromuscular block by decamethonium. Neither the tension of muscular twitch elicited by direct electrical stimulation to the muscle nor the resting membrane potentials of muscle fibers recorded intracellularly were affected by the enterotoxin. The enterotoxin (2.2 micrograms/ml) reduced the frequency, but not mean amplitude or amplitude distribution, of miniature end

  12. Block Scheduling. Research Brief

    ERIC Educational Resources Information Center

    Muir, Mike

    2003-01-01

    What are the effects of block scheduling? Results of transitioning from traditional to block scheduling are mixed. Some studies indicate no change in achievement results, nor change in teachers' opinions about instructional strategies. Other studies show that block scheduling doesn't work well for Advanced Placement or Music courses, that "hard to…

  13. Blocking and associability change.

    PubMed

    Jones, Peter M; Haselgrove, Mark

    2013-07-01

    Blocking of learning about a conditioned stimulus (the "blocked" cue) occurs when it is trained alongside an additional stimulus (the "blocking" cue) that has been previously presented with the outcome. A number of theories (e.g., N. J. Mackintosh. 1975a. A Theory of Attention: Variations in the Associability of Stimuli With Reinforcement. Psychological Review, 82, 276-298; J. M. Pearce & G. Hall. 1980. A Model for Pavlovian Learning: Variation in the Effectiveness of Conditioned But Not Unconditioned Stimuli. Psychological Review, 87, 532-552) account for this attenuation in learning by proposing that attention paid to the blocked cue is restricted. In three experiments, we examined the associability of both blocked and blocking cues. In Experiment 1, rats were trained with a blocking protocol before being given a test discrimination composed of two components; one of these components required the use of the previously blocked cue as a discriminative stimulus, and the other component was soluble by using the blocking cue. To our surprise, the component that depended on the blocked cue was more readily solved than the component dependent on the blocking cue. The results of Experiments 2 and 3 suggest that this is due to the quantity of exposure that each stimulus received during initial training. Implications for theories of blocking, and more widely associative learning, are discussed.

  14. Motor neuron apoptosis and neuromuscular junction perturbation are prominent features in a Drosophila model of Fus-mediated ALS

    PubMed Central

    2012-01-01

    Backgound Amyotrophic lateral sclerosis (ALS) is progressive neurodegenerative disease characterized by the loss of motor function. Several ALS genes have been identified as their mutations can lead to familial ALS, including the recently reported RNA-binding protein fused in sarcoma (Fus). However, it is not clear how mutations of Fus lead to motor neuron degeneration in ALS. In this study, we present a Drosophila model to examine the toxicity of Fus, its Drosophila orthologue Cabeza (Caz), and the ALS-related Fus mutants. Results Our results show that the expression of wild-type Fus/Caz or FusR521G induced progressive toxicity in multiple tissues of the transgenic flies in a dose- and age-dependent manner. The expression of Fus, Caz, or FusR521G in motor neurons significantly impaired the locomotive ability of fly larvae and adults. The presynaptic structures in neuromuscular junctions were disrupted and motor neurons in the ventral nerve cord (VNC) were disorganized and underwent apoptosis. Surprisingly, the interruption of Fus nuclear localization by either deleting its nuclear localization sequence (NLS) or adding a nuclear export signal (NES) blocked Fus toxicity. Moreover, we discovered that the loss of caz in Drosophila led to severe growth defects in the eyes and VNCs, caused locomotive disability and NMJ disruption, but did not induce apoptotic cell death. Conclusions These data demonstrate that the overexpression of Fus/Caz causes in vivo toxicity by disrupting neuromuscular junctions (NMJs) and inducing apoptosis in motor neurons. In addition, the nuclear localization of Fus is essential for Fus to induce toxicity. Our findings also suggest that Fus overexpression and gene deletion can cause similar degenerative phenotypes but the underlying mechanisms are likely different. PMID:22443542

  15. Interaction between protein kinase C and protein kinase A can modulate transmitter release at the rat neuromuscular synapse.

    PubMed

    Santafé, M M; Garcia, N; Lanuza, M A; Tomàs, M; Tomàs, J

    2009-02-15

    We used intracellular recording to investigate the functional interaction between protein kinase C (PKC) and protein kinase A (PKA) signal transduction cascades in the control of transmitter release in the neuromuscular synapses from adult rats. Our results indicate that: 1) PKA and PKC are independently involved in asynchronous release. 2) Evoked acetylcholine (ACh) release is enhanced with the PKA agonist Sp-8-BrcAMP and the PKC agonist phorbol ester (PMA). 3) PKA has a constitutive role in promoting a component of normal evoked transmitter release because, when the kinase is inhibited with H-89, the release diminishes. However, the PKC inhibitor calphostin C (CaC) does not affect ACh release. 4) PKA regulates neurotransmission without PKC involvement because, after PMA or CaC modulation of the PKC activity, coupling to the ACh release of PKA can normally be stimulated with Sp-8-BrcAMP or inhibited with H-89. 5) After PKA inhibition with H-89, PKC stimulation with PMA (or inhibition with CaC) does not lead to any change in evoked ACh release. However, in PKA-stimulated preparations with Sp-8-BrcAMP, PKC becomes tonically active, thus potentiating a component of release that can now be blocked with CaC. In normal conditions, therefore, PKA was able to modulate ACh release independently of PKC activity, whereas PKA stimulation caused the PKC coupling to evoked release. In contrast, PKA inhibition prevent PKC stimulation (with the phorbol ester) and coupling to ACh output. There was therefore some dependence of PKC on PKA activity in the fine control of the neuromuscular synaptic functionalism and ACh release.

  16. Muscarinic Ca2+ responses resistant to muscarinic antagonists at perisynaptic Schwann cells of the frog neuromuscular junction.

    PubMed Central

    Robitaille, R; Jahromi, B S; Charlton, M P

    1997-01-01

    1. Acetylcholine causes a rise of intracellular Ca2+ in perisynaptic Schwann cells (PSCs) of the frog neuromuscular junction. The signalling pathway was characterized using the fluorescent Ca2+ indicator fluo-3 and fluorescence microscopy. 2. Nicotinic antagonists had no effect on Ca2+ responses evoked by ACh and no Ca2+ responses were evoked with the nicotinic agonist nicotine. The muscarinic agonists muscarine and oxotremorine-M induced Ca2+ signals in PSCs. 3. Ca2+ responses remained unchanged when extracellular Ca2+ was removed, indicating that they are due to the release of Ca2+ from internal stores. Incubation with pertussis toxin did not alter the Ca2+ signals induced by muscarine, but did block depression of transmitter release induced by adenosine and prevented Ca2+ responses in PSCs induced by adenosine. 4. The general muscarinic antagonists atropine, quinuclidinyl benzilate and N-methyl-scopolamine failed to block Ca2+ responses to muscarinic agonists. Atropine (at 20,000-fold excess concentration) also failed to reduce the proportion of cells responding to a threshold muscarine concentration sufficient to cause responses in less than 50% of cells. Only the allosteric, non-specific blocker, gallamine (1-10 microM) was effective in blocking muscarine-induced Ca2+ responses. 5. In preparations denervated 7 days prior to experiments, low concentrations of atropine reversibly and completely blocked Ca2+ responses to muscarine. 6. The lack of blockade by general muscarinic antagonists in innervated, in situ preparations suggests that muscarinic Ca2+ responses at PSCs are not mediated by any of the five known muscarinic receptors or that post-translational modification prevented antagonist binding. Images Figure 2 Figure 3 Figure 4 Figure 6 Figure 7 PMID:9365908

  17. Impaired voluntary neuromuscular activation limits muscle power in mobility-limited older adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background. Age-related alterations of neuromuscular activation may contribute to deficits in muscle power and mobility function. This study assesses whether impaired activation of the agonist quadriceps and antagonist hamstrings, including amplitude- and velocity-dependent characteristics of activa...

  18. 31 CFR 594.201 - Prohibited transactions involving blocked property.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 106 of the USA PATRIOT Act of 2001 (Pub. L. 107-56, Oct. 26, 2001) amended section 203 of the... Attorney General, to have committed, or to pose a significant risk of committing, acts of terrorism that... act for or on behalf of, any person whose property or interests in property are blocked pursuant...

  19. Electrical stimulation for physiologic measurement of neuromuscular function and respiratory support during anticholinesterase poisoning. Annual report, October 1983-September 1984

    SciTech Connect

    Yodlowski, E.H.

    1984-10-01

    The purpose of this research is to develop the techniques necessary for providing short-term respiratory support for personnel poisoned by organophosphate agents. Following acute exposure to organophosphate compounds, respiration ceases before cardiovascular collapse occurs. Military personnel exposed to these compounds in the field are most likely to die from asphyxiation. By virtue of their ability to cross the blood-brain barrier and inhibit cholinesterase activity the organophosphates are capable of interrupting control of respiration either centrally (i.e. within the central nervous system) or peripherally by blocking neuromuscular transmission or contraction coupling at the peripheral muscles. We hypothesize that it will be possible to overcome organophosphate induced respiratory arrest by providing artificial respiratory pacing. This research is aimed at producing a means of respiratory support via electronic stimulation of the phrenic nerve (s) that can be used when central respiratory drive has become blocked by organophosphate agents. Animal experiments have been conducted to implement and evaluate the transesophageal electrophrenic stimulation technique (TEST) for respiratory pacing and to determine appropriate stimulation parameters to produce effective and efficient respirations.

  20. Neuromuscular activity of Bothrops alcatraz snake venom in chick biventer cervicis preparations.

    PubMed

    de Moraes, Delkia Seabra; Aparecido de Abreu, Valdemir; Rostelato-Ferreira, Sandro; Leite, Gildo B; Alice da Cruz-Höfling, Maria; Travaglia-Cardoso, Silvia R; Hyslop, Stephen; Rodrigues-Simioni, Léa

    2012-02-01

    Venom (10-100 μg/ml) from Bothrops alcatraz, a pitviper from the Alcatrazes Archipelago off the coast of southeastern Brazil, caused progressive, irreversible neuromuscular blockade in chick isolated biventer cervicis preparations. The venom also inhibited contractures to exogenous ACh (110 μM) and KCl (20 mM), caused myofiber damage and increased creatine kinase release. Commercial bothropic antivenom raised against mainland Bothrops species neutralized the neuromuscular activity, depending on the venom concentration. PMID:22155137

  1. Update on neuromuscular disorders in pediatric orthopaedics: Duchenne muscular dystrophy, myelomeningocele, and cerebral palsy.

    PubMed

    Chambers, Henry G

    2014-01-01

    The purpose of this seminar was to review a large range of lower extremity and neuromuscular disorders. Because of the diversity of the topics covered, including clubfoot and vertical talus treatment, management of Legg-Calve-Perthes disease, and limb lengthening in dwarfism, this review will focus on the neuromuscular subsection reviewing the current management of the muscular dystrophies, myelomeningocele, and cerebral palsy. PMID:25207736

  2. Presynaptic and postsynaptic effects of the venom of the Australian tiger snake at the neuromuscular junction

    PubMed Central

    Datyner, M. E.; Gage, P. W.

    1973-01-01

    1. Crude venom (TSV) from the Australian tiger snake (Notechis scutatus scutatus) has both presynaptic and postsynaptic effects at the neuromuscular junctions of toads. 2. TSV (50 μg/ml) rapidly blocked indirectly elicited muscle twitches without affecting the compound action potential in the sciatic nerve or twitches elicited by direct stimulation. 3. Low concentrations of the venom (1-10 μg/ml) reduced the amplitude of miniature endplate potentials (m.e.p.ps) and inhibited the depolarization of muscle fibres normally caused by carbachol. It was concluded that a fraction of the venom binds to acetylcholine receptors. 4. The frequency of m.e.p.ps was at first increased by TSV at a concentration of 1 μg/ml. Occasional, high frequency `bursts' of m.e.p.ps were recorded in some preparations. The mean frequency of m.e.p.ps appeared to fall after several hours in the venom. 5. The quantal content of endplate potentials (e.p.ps) was reduced by the venom. With low concentrations (1 μg/ml), an initial increase in quantal content was often seen. When the quantal content was markedly depressed there was no parallel reduction in the amplitude of nerve terminal spikes recorded extracellularly, though a later fall in size and slowing of time course was often seen. 6. There was evidence that TSV eventually changed the normal Poisson characteristics of the spontaneous release of quanta and this may be correlated with electronmicroscopic changes in nerve terminals. 7. Tiger snake antivenene counteracted the postsynaptic, but not the presynaptic effects of TSV when they had developed. PMID:4367126

  3. Block LU factorization

    NASA Technical Reports Server (NTRS)

    Demmel, James W.; Higham, Nicholas J.; Schreiber, Robert S.

    1992-01-01

    Many of the currently popular 'block algorithms' are scalar algorithms in which the operations have been grouped and reordered into matrix operations. One genuine block algorithm in practical use is block LU factorization, and this has recently been shown by Demmel and Higham to be unstable in general. It is shown here that block LU factorization is stable if A is block diagonally dominant by columns. Moreover, for a general matrix the level of instability in block LU factorization can be founded in terms of the condition number kappa(A) and the growth factor for Gaussian elimination without pivoting. A consequence is that block LU factorization is stable for a matrix A that is symmetric positive definite or point diagonally dominant by rows or columns as long as A is well-conditioned.

  4. Effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction

    PubMed Central

    Shim, Jae-Kwang; Choi, Ho-Suk; Shin, Jun-Ho

    2015-01-01

    [Purpose] This study examined the effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction. [Subjects and Methods] The subjects were 16 adults who underwent arthroscopic anterior cruciate reconstruction and neuromuscular training. The Lysholm scale was used to assess functional disorders on the affected knee joint. A KT-2000 arthrometer was used to measure anterior displacement of the tibia against the femur. Surface electromyography was used to detect the muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus before and after neuromuscular training. [Results] There was significant relaxation in tibial anterior displacement of the affected and sound sides in the supine position before neuromuscular training. Furthermore, the difference in the tibial anterior displacement of the affected knee joints in the standing position was reduced after neuromuscular training. Moreover, the variation of the muscle activation evoked higher muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus. [Conclusion] Neuromuscular training may improve functional joint stability in patients with orthopedic musculoskeletal injuries in the postoperative period. PMID:26834316

  5. Effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction.

    PubMed

    Shim, Jae-Kwang; Choi, Ho-Suk; Shin, Jun-Ho

    2015-12-01

    [Purpose] This study examined the effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction. [Subjects and Methods] The subjects were 16 adults who underwent arthroscopic anterior cruciate reconstruction and neuromuscular training. The Lysholm scale was used to assess functional disorders on the affected knee joint. A KT-2000 arthrometer was used to measure anterior displacement of the tibia against the femur. Surface electromyography was used to detect the muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus before and after neuromuscular training. [Results] There was significant relaxation in tibial anterior displacement of the affected and sound sides in the supine position before neuromuscular training. Furthermore, the difference in the tibial anterior displacement of the affected knee joints in the standing position was reduced after neuromuscular training. Moreover, the variation of the muscle activation evoked higher muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus. [Conclusion] Neuromuscular training may improve functional joint stability in patients with orthopedic musculoskeletal injuries in the postoperative period.

  6. ACT: Acting Out Central Theme.

    ERIC Educational Resources Information Center

    Kise, Joan Duff

    1982-01-01

    The author describes ACT (Acting Out Central Theme), a method for dealing with psychomotor, cognitive, and affective domains in slow readers. The ACT approach involves three sessions which focus on discussion of a theme such as friendship, presentaton of the theme as a skit, and assignment of topics to individual students. (SW)

  7. Biochemical and genetic analysis of butyrylcholinesterase (BChE) in a family, due to prolonged neuromuscular blockade after the use of succinylcholine

    PubMed Central

    Garcia, Daniel Fantozzi; Oliveira, Ticiano G.; Molfetta, Greice A.; Garcia, Luiz V.; Ferreira, Cristiane A.; Marques, Adriana A.; Silva, Wilson Araujo

    2011-01-01

    Butyrylcholinesterase (BChE) is a plasma enzyme that catalyzes the hydrolysis of choline esters, including the muscle-relaxant succinylcholine and mivacurium. Patients who present sustained neuromuscular blockade after using succinylcholine usually carry BChE variants with reduced enzyme activity or an acquired BChE deficiency. We report here the molecular basis of the BCHE gene underlying the slow catabolism of succinylcholine in a patient who underwent endoscopic nasal surgery. We measured the enzyme activity of BChE and extracted genomic DNA in order to study the promoter region and all exons of the BCHE gene of the patient, her parents and siblings. PCR products were sequenced and compared with reference sequences from GenBank. We detected that the patient and one of her brothers have two homozygous mutations: nt1615 GCA > ACA (Ala539Thr), responsible for the K variant, and nt209 GAT > GGT (Asp70Gly), which produces the atypical variant A. Her parents and two of her brothers were found to be heterozygous for the AK allele, and another brother is homozygous for the normal allele. Sequence analysis of exon 1 including 5′UTR showed that the proband and her brother are homozygous for –116GG. The AK/AK genotype is considered the most frequent in hereditary hypocholinesterasemia (44%). This work demonstrates the importance of defining the phenotype and genotype of the BCHE gene in patients who are subjected to neuromuscular block by succinylcholine, because of the risk of prolonged neuromuscular paralysis. PMID:21637541

  8. Synaptic Deficits at Neuromuscular Junctions in Two Mouse Models of Charcot–Marie–Tooth Type 2d

    PubMed Central

    Spaulding, Emily L.; Sleigh, James N.; Morelli, Kathryn H.; Pinter, Martin J.; Burgess, Robert W.

    2016-01-01

    Patients with Charcot–Marie–Tooth Type 2D (CMT2D), caused by dominant mutations in Glycl tRNA synthetase (GARS), present with progressive weakness, consistently in the hands, but often in the feet also. Electromyography shows denervation, and patients often report that early symptoms include cramps brought on by cold or exertion. Based on reported clinical observations, and studies of mouse models of CMT2D, we sought to determine whether weakened synaptic transmission at the neuromuscular junction (NMJ) is an aspect of CMT2D. Quantal analysis of NMJs in two different mouse models of CMT2D (GarsP278KY, GarsC201R), found synaptic deficits that correlated with disease severity and progressed with age. Results of voltage-clamp studies revealed presynaptic defects characterized by: (1) decreased frequency of spontaneous release without any change in quantal amplitude (miniature endplate current), (2) reduced amplitude of evoked release (endplate current) and quantal content, (3) age-dependent changes in the extent of depression in response to repetitive stimulation, and (4) release failures at some NMJs with high-frequency, long-duration stimulation. Drugs that modify synaptic efficacy were tested to see whether neuromuscular performance improved. The presynaptic action of 3,4 diaminopyridine was not beneficial, whereas postsynaptic-acting physostigmine did improve performance. Smaller mutant NMJs with correspondingly fewer vesicles and partial denervation that eliminates some release sites also contribute to the reduction of release at a proportion of mutant NMJs. Together, these voltage-clamp data suggest that a number of release processes, while essentially intact, likely operate suboptimally at most NMJs of CMT2D mice. SIGNIFICANCE STATEMENT We have uncovered a previously unrecognized aspect of axonal Charcot–Marie–Tooth disease in mouse models of CMT2D. Synaptic dysfunction contributes to impaired neuromuscular performance and disease progression. This

  9. Presynaptic action of trifluoperazine at the frog neuromuscular junction.

    PubMed

    Publicover, S J

    1983-02-01

    Treatment of frog neuromuscular preparations bathed in basic frog saline (1.8 mM Ca2+) with trifluoperazine (25 microM) caused an increase in MEPP frequency in 6 out of 10 preparations tested. The mean normalised MEPP frequency after 15 min of treatment was approximately 1.5. 10 microM trifluoperazine had a similar effect. In salines containing low concentrations of Ca2+ (50 microM Ca2+, 2 mM Mg2+ or 0 Ca2+, 1 mM EGTA) the stimulatory action of trifluoperazine was more marked and occurred in a higher proportion of the preparations tested (11 out of 14). When evoked release of transmitter was reduced to very low levels by Mg2+-containing salines treatment with trifluoperazine (2.5-25 microM) caused an increase in quantal content of 20-60%. Depolarisation of preparations bathed in standard frog saline by increasing [K+]o to 10 mM resulted in a 10-fold increase in MEPP frequency. This response was inhibited by about 25% in 10 microM trifluoperazine and by about 45% in 25 microM trifluoperazine. Pre-treatment of preparations with trifluoperazine (25 microM) caused a marked reduction in the response of MEPP frequency to tetanic stimulation (50 Hz) both in the presence of an inward electrochemical gradient for Ca2+ (50 microM Ca2+, 2 mM Mg2+) and in a Ca2+-free saline (0 Ca2+, 1 mM EGTA). The effects of trifluoperazine on tetanic enhancement of MEPP frequency are compared to those of other agents and it is shown that the results are inconsistent with an effect of the drug on Ca2+-fluxes at the plasma membrane. It is concluded that trifluoperazine has both stimulatory and inhibitory effects on transmitter release at the frog neuromuscular junction and that the inhibitory effect is probably due to inhibition of excitation-secretion coupling at a point subsequent to Ca2+ mobilization.

  10. TMEM184b Promotes Axon Degeneration and Neuromuscular Junction Maintenance

    PubMed Central

    Geisler, Stefanie; Pittman, Sara K.; Doan, Ryan A.; Weihl, Conrad C.; Milbrandt, Jeffrey; DiAntonio, Aaron

    2016-01-01

    Complex nervous systems achieve proper connectivity during development and must maintain these connections throughout life. The processes of axon and synaptic maintenance and axon degeneration after injury are jointly controlled by a number of proteins within neurons, including ubiquitin ligases and mitogen activated protein kinases. However, our understanding of these molecular cascades is incomplete. Here we describe the phenotype resulting from mutation of TMEM184b, a protein identified in a screen for axon degeneration mediators. TMEM184b is highly expressed in the mouse nervous system and is found in recycling endosomes in neuronal cell bodies and axons. Disruption of TMEM184b expression results in prolonged maintenance of peripheral axons following nerve injury, demonstrating a role for TMEM184b in axon degeneration. In contrast to this protective phenotype in axons, uninjured mutant mice have anatomical and functional impairments in the peripheral nervous system. Loss of TMEM184b causes swellings at neuromuscular junctions that become more numerous with age, demonstrating that TMEM184b is critical for the maintenance of synaptic architecture. These swellings contain abnormal multivesicular structures similar to those seen in patients with neurodegenerative disorders. Mutant animals also show abnormal sensory terminal morphology. TMEM184b mutant animals are deficient on the inverted screen test, illustrating a role for TMEM184b in sensory-motor function. Overall, we have identified an important function for TMEM184b in peripheral nerve terminal structure, function, and the axon degeneration pathway. SIGNIFICANCE STATEMENT Our work has identified both neuroprotective and neurodegenerative roles for a previously undescribed protein, TMEM184b. TMEM184b mutation causes delayed axon degeneration following peripheral nerve injury, indicating that it participates in the degeneration process. Simultaneously, TMEM184b mutation causes progressive structural

  11. miR-30e Blocks Autophagy and Acts Synergistically with Proanthocyanidin for Inhibition of AVEN and BIRC6 to Increase Apoptosis in Glioblastoma Stem Cells and Glioblastoma SNB19 Cells.

    PubMed

    Chakrabarti, Mrinmay; Klionsky, Daniel J; Ray, Swapan K

    2016-01-01

    Glioblastoma is the most common and malignant brain tumor in humans. It is a heterogeneous tumor harboring glioblastoma stem cells (GSC) and other glioblastoma cells that survive and sustain tumor growth in a hypoxic environment via induction of autophagy and resistance to apoptosis. So, a therapeutic strategy to inhibit autophagy and promote apoptosis could greatly help control growth of glioblastoma. We created hypoxia using sodium sulfite (SS) for induction of substantiated autophagy in human GSC and glioblastoma SNB19 cells. Induction of autophagy was confirmed by acridine orange (AO) staining and significant increase in Beclin-1 in autophagic cells. microRNA database (miRDB) search suggested that miR-30e could suppress the autophagy marker Beclin-1 and also inhibit the caspase activation inhibitors (AVEN and BIRC6). Pro-apoptotic effect of proanthocyanidin (PAC) has not yet been explored in glioblastoma cells. Combination of 50 nM miR-30e and 150 μM PAC acted synergistically for inhibition of viability in both cells. This combination therapy most effectively altered expression of molecules for inhibition of autophagy and induced extrinsic and intrinsic pathways of apoptosis through suppression of AVEN and BIRC6. Collectively, combination of miR-30e and PAC is a promising therapeutic strategy to inhibit autophagy and increase apoptosis in GSC and SNB19 cells. PMID:27388765

  12. miR-30e Blocks Autophagy and Acts Synergistically with Proanthocyanidin for Inhibition of AVEN and BIRC6 to Increase Apoptosis in Glioblastoma Stem Cells and Glioblastoma SNB19 Cells

    PubMed Central

    Chakrabarti, Mrinmay; Klionsky, Daniel J.; Ray, Swapan K.

    2016-01-01

    Glioblastoma is the most common and malignant brain tumor in humans. It is a heterogeneous tumor harboring glioblastoma stem cells (GSC) and other glioblastoma cells that survive and sustain tumor growth in a hypoxic environment via induction of autophagy and resistance to apoptosis. So, a therapeutic strategy to inhibit autophagy and promote apoptosis could greatly help control growth of glioblastoma. We created hypoxia using sodium sulfite (SS) for induction of substantiated autophagy in human GSC and glioblastoma SNB19 cells. Induction of autophagy was confirmed by acridine orange (AO) staining and significant increase in Beclin-1 in autophagic cells. microRNA database (miRDB) search suggested that miR-30e could suppress the autophagy marker Beclin-1 and also inhibit the caspase activation inhibitors (AVEN and BIRC6). Pro-apoptotic effect of proanthocyanidin (PAC) has not yet been explored in glioblastoma cells. Combination of 50 nM miR-30e and 150 μM PAC acted synergistically for inhibition of viability in both cells. This combination therapy most effectively altered expression of molecules for inhibition of autophagy and induced extrinsic and intrinsic pathways of apoptosis through suppression of AVEN and BIRC6. Collectively, combination of miR-30e and PAC is a promising therapeutic strategy to inhibit autophagy and increase apoptosis in GSC and SNB19 cells. PMID:27388765

  13. Efficacy of pulsed low-intensity electric neuromuscular stimulation in reducing pain and disability in patients with myofascial syndrome.

    PubMed

    Iodice, P; Lessiani, G; Franzone, G; Pezzulo, G

    2016-01-01

    Myofascial pain syndrome (MPS) is characterized by chronic pain in multiple myofascial trigger points and fascial constrictions. In recent years, the scientific literature has recognized the need to include the patient with MPS in a multidimensional rehabilitation project. At the moment, the most widely recognized therapeutic methods for the treatment of myofascial syndrome include the stretch and spray pressure massage. Microcurrent electric neuromuscular stimulation was proposed in pain management for its effects on normalizing bioelectricity of cells and for its sub-sensory application. In this study, we tested the efficacy of low-intensity pulsed electric neuromuscular stimulus (PENS) on pain in patients with MPS of cervical spine muscles. We carried out a prospective-analytic longitudinal study at an outpatient clinic during two weeks. Forty subjects (mean age 42±13 years) were divided into two groups: treatment (TrGr, n=20) and control group (CtrlGr, n=20). Visual-analog scale (VAS) values, concerning the spontaneous and movement-related pain in the cervical-dorsal region at baseline (T0) and at the end of the study (T1), showed a reduction from 7 to 3.81 (p < 0.001) in TrGr. In the CtrlGr, VAS was reduced from 8.2 to 7.2 (n.s.). Moreover, the pressure pain threshold at T0 was 2.1 vs 4.2 at T1 (p < 0.001) in TrG. In the CtrlGR we observed no significant changes. Modulated low-intensity PENS is an innovative therapy permitting to act on the transmission of pain and on the restoration of tissue homeostasis. It seems to affect the transmission of pain through the stimulation of A-beta fibers. The above results show that low-intensity PENS can be considered as an effective treatment to reduce pain and disability in patients with MPS.

  14. Efficacy of pulsed low-intensity electric neuromuscular stimulation in reducing pain and disability in patients with myofascial syndrome.

    PubMed

    Iodice, P; Lessiani, G; Franzone, G; Pezzulo, G

    2016-01-01

    Myofascial pain syndrome (MPS) is characterized by chronic pain in multiple myofascial trigger points and fascial constrictions. In recent years, the scientific literature has recognized the need to include the patient with MPS in a multidimensional rehabilitation project. At the moment, the most widely recognized therapeutic methods for the treatment of myofascial syndrome include the stretch and spray pressure massage. Microcurrent electric neuromuscular stimulation was proposed in pain management for its effects on normalizing bioelectricity of cells and for its sub-sensory application. In this study, we tested the efficacy of low-intensity pulsed electric neuromuscular stimulus (PENS) on pain in patients with MPS of cervical spine muscles. We carried out a prospective-analytic longitudinal study at an outpatient clinic during two weeks. Forty subjects (mean age 42±13 years) were divided into two groups: treatment (TrGr, n=20) and control group (CtrlGr, n=20). Visual-analog scale (VAS) values, concerning the spontaneous and movement-related pain in the cervical-dorsal region at baseline (T0) and at the end of the study (T1), showed a reduction from 7 to 3.81 (p < 0.001) in TrGr. In the CtrlGr, VAS was reduced from 8.2 to 7.2 (n.s.). Moreover, the pressure pain threshold at T0 was 2.1 vs 4.2 at T1 (p < 0.001) in TrG. In the CtrlGR we observed no significant changes. Modulated low-intensity PENS is an innovative therapy permitting to act on the transmission of pain and on the restoration of tissue homeostasis. It seems to affect the transmission of pain through the stimulation of A-beta fibers. The above results show that low-intensity PENS can be considered as an effective treatment to reduce pain and disability in patients with MPS. PMID:27358158

  15. Agrin acts via a MuSK receptor complex.

    PubMed

    Glass, D J; Bowen, D C; Stitt, T N; Radziejewski, C; Bruno, J; Ryan, T E; Gies, D R; Shah, S; Mattsson, K; Burden, S J; DiStefano, P S; Valenzuela, D M; DeChiara, T M; Yancopoulos, G D

    1996-05-17

    Formation of th neuromuscular junction depends upon reciprocal inductive interactions between the developing nerve and muscle, resulting in the precise juxtaposition of a differentiated nerve terminal with a highly specialized patch on the muscle membrane, termed the motor endplate. Agrin is a nerve-derived factor that can induced molecular reorganizations at the motor endplate, but the mechanism of action of agrin remains poorly understood. MuSK is a receptor tyrosine kinase localized to the motor endplate, seemingly well positioned to receive a key nerve-derived signal. Mice lacking either agrin or MuSK have recently been generated and exhibit similarly profound defects in their neuromuscular junctions. Here we demonstrate that agrin acts via a receptor complex that includes MuSK as well as a myotube-specific accessory component.

  16. Island custom blocking technique

    SciTech Connect

    Carabetta, R.J. )

    1988-03-01

    The technique of Island blocking is being used more frequently since the advent of our new head and neck blocking techniques and the implementation of a newly devised lung protocol. The system presented affords the mould room personnel a quick and accurate means of island block fabrication without the constant remeasuring or subtle shifting to approximate correct placement. The cookie cutter is easily implemented into any department's existing block cutting techniques. The device is easily and inexpensively made either in a machine shop or acquired by contacting the author.

  17. Protein based Block Copolymers

    PubMed Central

    Rabotyagova, Olena S.; Cebe, Peggy; Kaplan, David L.

    2011-01-01

    Advances in genetic engineering have led to the synthesis of protein-based block copolymers with control of chemistry and molecular weight, resulting in unique physical and biological properties. The benefits from incorporating peptide blocks into copolymer designs arise from the fundamental properties of proteins to adopt ordered conformations and to undergo self-assembly, providing control over structure formation at various length scales when compared to conventional block copolymers. This review covers the synthesis, structure, assembly, properties, and applications of protein-based block copolymers. PMID:21235251

  18. Verifax: Biometric instruments measuring neuromuscular disorders/performance impairments

    NASA Astrophysics Data System (ADS)

    Morgenthaler, George W.; Shrairman, Ruth; Landau, Alexander

    1998-01-01

    VeriFax, founded in 1990 by Dr. Ruth Shrairman and Mr. Alex Landau, began operations with the aim of developing a biometric tool for the verification of signatures from a distance. In the course of developing this VeriFax Autograph technology, two other related applications for the technologies under development at VeriFax became apparent. The first application was in the use of biometric measurements as clinical monitoring tools for physicians investigating neuromuscular diseases (embodied in VeriFax's Neuroskill technology). The second application was to evaluate persons with critical skills (e.g., airline pilots, bus drivers) for physical and mental performance impairments caused by stress, physiological disorders, alcohol, drug abuse, etc. (represented by VeriFax's Impairoscope prototype instrument). This last application raised the possibility of using a space-qualified Impairoscope variant to evaluate astronaut performance with respect to the impacts of stress, fatigue, excessive workload, build-up of toxic chemicals within the space habitat, etc. The three applications of VeriFax's patented technology are accomplished by application-specific modifications of the customized VeriFax software. Strong commercial market potentials exist for all three VeriFax technology applications, and market progress will be presented in more detail below.

  19. Applications of shape memory alloys for neurology and neuromuscular rehabilitation.

    PubMed

    Pittaccio, Simone; Garavaglia, Lorenzo; Ceriotti, Carlo; Passaretti, Francesca

    2015-01-01

    Shape memory alloys (SMAs) are a very promising class of metallic materials that display interesting nonlinear properties, such as pseudoelasticity (PE), shape memory effect (SME) and damping capacity, due to high mechanical hysteresis and internal friction. Our group has applied SMA in the field of neuromuscular rehabilitation, designing some new devices based on the mentioned SMA properties: in particular, a new type of orthosis for spastic limb repositioning, which allows residual voluntary movement of the impaired limb and has no predetermined final target position, but follows and supports muscular elongation in a dynamic and compliant way. Considering patients in the sub-acute phase after a neurological lesion, and possibly bedridden, the paper presents a mobiliser for the ankle joint, which is designed exploiting the SME to provide passive exercise to the paretic lower limb. Two different SMA-based applications in the field of neuroscience are then presented, a guide and a limb mobiliser specially designed to be compatible with diagnostic instrumentations that impose rigid constraints in terms of electromagnetic compatibility and noise distortion. Finally, the paper discusses possible uses of these materials in the treatment of movement disorders, such as dystonia or hyperkinesia, where their dynamic characteristics can be advantageous. PMID:26023790

  20. Applications of Shape Memory Alloys for Neurology and Neuromuscular Rehabilitation

    PubMed Central

    Pittaccio, Simone; Garavaglia, Lorenzo; Ceriotti, Carlo; Passaretti, Francesca

    2015-01-01

    Shape memory alloys (SMAs) are a very promising class of metallic materials that display interesting nonlinear properties, such as pseudoelasticity (PE), shape memory effect (SME) and damping capacity, due to high mechanical hysteresis and internal friction. Our group has applied SMA in the field of neuromuscular rehabilitation, designing some new devices based on the mentioned SMA properties: in particular, a new type of orthosis for spastic limb repositioning, which allows residual voluntary movement of the impaired limb and has no predetermined final target position, but follows and supports muscular elongation in a dynamic and compliant way. Considering patients in the sub-acute phase after a neurological lesion, and possibly bedridden, the paper presents a mobiliser for the ankle joint, which is designed exploiting the SME to provide passive exercise to the paretic lower limb. Two different SMA-based applications in the field of neuroscience are then presented, a guide and a limb mobiliser specially designed to be compatible with diagnostic instrumentations that impose rigid constraints in terms of electromagnetic compatibility and noise distortion. Finally, the paper discusses possible uses of these materials in the treatment of movement disorders, such as dystonia or hyperkinesia, where their dynamic characteristics can be advantageous. PMID:26023790

  1. Organelle pathology in metabolic neuromuscular disease: an overview.

    PubMed Central

    Becker, L E

    1990-01-01

    The spectrum of metabolic neuromuscular disorders is wide. Most inherited metabolic diseases are related to enzyme defects within lysosomes but recent advances emphasize abnormalities of mitochondria, peroxisomes and intermediate filaments. In this overview, organelle pathology is described in the context of both the clinical manifestations and the biochemical and/or molecular aspects of the disease. Among the many clinical presentations of mitochondrial disorders three emerge as distinctive entities: mitochondrial encephalopathy with lactic acidosis and stroke-like symptoms, mitochondrial encephalopathy with ragged-red fibers, and Kearns-Sayre syndrome. Peroxisomal disorders are associated with numerous biochemical defects, the most frequent of which are Zellweger's syndrome, neonatal adrenoleukodystrophy, and infantile Refsum's disease. Disorders of cytoskeletal proteins are associated with distinctive pathological accumulation of intermediate filaments but are without confirmed evidence of a biochemical defect. Understanding the role that organelle pathology plays in the pathogenesis of cellular disturbance or demise is essential to the elucidation of the pathogenesis of metabolic disorders. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10. PMID:2407327

  2. Regional neuromuscular regulation within human rectus femoris muscle during gait.

    PubMed

    Watanabe, Kohei; Kouzaki, Motoki; Moritani, Toshio

    2014-11-01

    The spatial distribution pattern of neuromuscular activation within the human rectus femoris (RF) muscle was investigated during gait by multi-channel surface electromyography (surface EMG). Eleven healthy men walked on a treadmill with three gait speeds (4, 5, and 6 km/h) and gradients (0°, 12.5°, and 25°). The spatial distribution of surface EMG was tested by central locus activation (CLA), which is calculated from 2-D multi-channel surface EMG with 46 surface electrodes. For all conditions, CLA was around the middle regions during the swing-to-stance transition and moved in a proximal direction during the stance phase and stance-to-swing transition (p<0.05). CLA during the stance-to-swing transition and early swing phase significantly moved to proximal site with increasing gait speed (p<0.05). During the early stance and swing phases, with increasing grade, CLA significantly moved distally (p<0.05). These results suggest that the RF muscle is regionally activated during a gait cycle and is non-uniformly regulated longitudinally.

  3. Stabilization of human standing posture using functional neuromuscular stimulation.

    PubMed

    Soetanto, D; Kuo, C Y; Babic, D

    2001-12-01

    Functional neuromuscular stimulation (FNS)/functional electrical stimulation (FES) is a potential way to restore some functionality to the limbs of patients with spinal cord injury through direct/indirect stimulation of the motoneuron. One of the constraints for wider use of FNS on paraplegic patients is the lack of efficient control algorithm. Most of the published works on FNS/FES control are based on oversimplified models of human body dynamics. An innovative control strategy for stabilizing the standing posture of paraplegic patients is proposed here which is a combination of a proportional-plus-derivative controller for motions of the skeletal system and a control action prediction mechanism to produce musculotendon activation. The goal is to produce musculotendon torque which can approximate those demanded by the controller for the skeletal system. In computer simulations, using a detailed skeletal-musculotendon-muscle activation dynamics model of human body, this FNS/FES control approach can stabilize a paraplegic patient's standing posture with the minimum number of musculotendon groups. Also, it is found that this control strategy can maintain stability even in the presence of reasonable variations in the controller's musculotendon parameters.

  4. Neuromuscular synaptic function in mice lacking major subsets of gangliosides.

    PubMed

    Zitman, F M P; Todorov, B; Jacobs, B C; Verschuuren, J J; Furukawa, K; Furukawa, K; Willison, H J; Plomp, J J

    2008-10-28

    Gangliosides are a family of sialylated glycosphingolipids enriched in the outer leaflet of neuronal membranes, in particular at synapses. Therefore, they have been hypothesized to play a functional role in synaptic transmission. We have measured in detail the electrophysiological parameters of synaptic transmission at the neuromuscular junction (NMJ) ex vivo of a GD3-synthase knockout mouse, expressing only the O- and a-series gangliosides, as well as of a GM2/GD2-synthase*GD3-synthase double-knockout (dKO) mouse, lacking all gangliosides except GM3. No major synaptic deficits were found in either null-mutant. However, some extra degree of rundown of acetylcholine release at high intensity use was present at the dKO NMJ and a temperature-specific increase in acetylcholine release at 35 degrees C was observed in GD3-synthase knockout NMJs, compared with wild-type. These results indicate that synaptic transmission at the NMJ is not crucially dependent on the particular presence of most ganglioside family members and remains largely intact in the sole presence of GM3 ganglioside. Rather, presynaptic gangliosides appear to play a modulating role in temperature- and use-dependent fine-tuning of transmitter output. PMID:18801416

  5. Using factor analysis to identify neuromuscular synergies during treadmill walking

    NASA Technical Reports Server (NTRS)

    Merkle, L. A.; Layne, C. S.; Bloomberg, J. J.; Zhang, J. J.

    1998-01-01

    Neuroscientists are often interested in grouping variables to facilitate understanding of a particular phenomenon. Factor analysis is a powerful statistical technique that groups variables into conceptually meaningful clusters, but remains underutilized by neuroscience researchers presumably due to its complicated concepts and procedures. This paper illustrates an application of factor analysis to identify coordinated patterns of whole-body muscle activation during treadmill walking. Ten male subjects walked on a treadmill (6.4 km/h) for 20 s during which surface electromyographic (EMG) activity was obtained from the left side sternocleidomastoid, neck extensors, erector spinae, and right side biceps femoris, rectus femoris, tibialis anterior, and medial gastrocnemius. Factor analysis revealed 65% of the variance of seven muscles sampled aligned with two orthogonal factors, labeled 'transition control' and 'loading'. These two factors describe coordinated patterns of muscular activity across body segments that would not be evident by evaluating individual muscle patterns. The results show that factor analysis can be effectively used to explore relationships among muscle patterns across all body segments to increase understanding of the complex coordination necessary for smooth and efficient locomotion. We encourage neuroscientists to consider using factor analysis to identify coordinated patterns of neuromuscular activation that would be obscured using more traditional EMG analyses.

  6. Development of neuromuscular organization in the ctenophore Pleurobrachia bachei.

    PubMed

    Norekian, Tigran P; Moroz, Leonid L

    2016-01-01

    The phylogenetic position of the phylum Ctenophora and the nature of ctenphore nervous systems are highly debated topics in modern evolutionary biology. However, very little is known about the organization of ctenophore neural and muscular systems, and virtually nothing has been reported about their embryogenesis. Here we have characterized the neural and muscular development of the sea gooseberry, Pleurobrachia bachei, starting from the cleavage stages to posthatching larvae. Scanning electron microscopy and immunochemistry were used to describe the formation of the embryonic mouth, tentacles, combs, aboral organ, and putative sensory cells. The muscles started their specification at the end of the first day of Pleurobrachia development. In contrast, neurons appeared 2 days after myogenesis, just before the hatching of fully formed cydippid larvae. The first tubulin-immunoreactive neurons, a small group of four to six cells with neuronal processes, was initially recognized at the aboral pole during the third day of development. Surprisingly, this observed neurogenesis occurred after the emergence of distinct behavioral patterns in the embryos. Thus, the embryonic behavior associated with comb cilia beatings and initial muscle organization does not require morphologically defined neurons and their elongated neurites. This study provides the first description of neuromuscular development in the enigmatic ctenophores and establishes the foundation for future research using emerging genomic tools and resources. PMID:26105692

  7. A single-channel implantable microstimulator for functional neuromuscular stimulation.

    PubMed

    Ziaie, B; Nardin, M D; Coghlan, A R; Najafi, K

    1997-10-01

    This paper describes a single-channel implantable microstimulator for functional neuromuscular stimulation. This device measures 2 x 2 x 10 mm3 and can be inserted into paralyzed muscle groups by expulsion from a hypodermic needle. Power and data to the device are supplied from outside by RF telemetry using an amplitude-modulated 2-MHz RF carrier generated using a high-efficiency class-E transmitter. The transmitted signal carries a 5-b address which selects one of the 32 possible microstimulators. The selected device then delivers up to 2 microC of charge store in a tantalum chip capacitor for up to 200 microseconds (10 mA) into loads of < 800 omega through a high-current thin-film iridium-oxide (IrOx) electrode (approximately 0.3 mm2 in area). A bi-CMOS receiver circuitry is used to: generate two regulated voltage supplies (4.5 and 9 V), recover a 2-MHz clock from the carrier, demodulate the address code, and activate the output current delivery circuitry upon the reception of an external command. The overall power dissipation of the receiver circuitry is 45-55 mW. The implant is hermetically packaged using a custom-made glass capsule.

  8. Safe neuromuscular electrical stimulator designed for the elderly.

    PubMed

    Krenn, Matthias; Haller, Michael; Bijak, Manfred; Unger, Ewald; Hofer, Christian; Kern, Helmut; Mayr, Winfried

    2011-03-01

    A stimulator for neuromuscular electrical stimulation (NMES) was designed, especially suiting the requirements of elderly people with reduced cognitive abilities and diminished fine motor skills. The aging of skeletal muscle is characterized by a progressive decline in muscle mass, force, and condition. Muscle training with NMES reduces the degradation process. The discussed system is intended for evoked muscle training of the anterior and posterior thigh. The core of the stimulator is based on a microcontroller with two modular output stages. The system has two charge-balanced biphasic voltage-controlled stimulation channels. Additionally, the evoked myoelectric signal (M-wave) and the myokinematic signal (surface acceleration) are measured. A central controller unit allows using the stimulator as a stand-alone device. To set up the training sequences and to evaluate the compliance data, a personal computer is connected to the stimulator via a universal serial bus. To help elderly people handle the stimulator by themselves, the user interface is kept very simple. For safety reasons, the electrode impedance is monitored during stimulation. A comprehensive compliance management with included measurements of muscle activity and stimulation intensity enables a scientific use of the stimulator in clinical trials.

  9. Effects of two neuromuscular fatigue protocols on landing performance.

    PubMed

    James, C Roger; Scheuermann, Barry W; Smith, Michael P

    2010-08-01

    The purpose of the study was to investigate the effects of two fatigue protocols on landing performance. A repeated measures design was used to examine the effects of fatigue and fatigue protocol on neuromuscular and biomechanical performance variables. Ten volunteers performed non-fatigued and fatigued landings on two days using different fatigue protocols. Repeated maximum isometric squats were used to induce fatigue on day one. Sub-maximum cycling was used to induce fatigue on day two. Isometric squat maximum voluntary contraction (MVC) was measured before and after fatigued landings on each day. During the landings, ground reaction force (GRF), knee kinematics, and electromyographic (EMG) data were recorded. Isometric MVC, GRF peaks, loading rates, impulse, knee flexion at contact, range of motion, max angular velocity, and EMG root mean square (RMS) values were compared pre- and post-fatiguing exercise and between fatigue protocols using repeated ANOVA. Fatigue decreased MVC strength (p0.05), GRF second peak, and initial impulse (p0.01), but increased quadriceps medium latency stretch reflex EMG activity (p0.012). Knee flexion at contact was 5.2 degrees greater (p0.05) during fatigued landings following the squat exercise compared to cycling. Several variables exhibited non-significant but large effect sizes when comparing the effects of fatigue and fatigue protocol. In conclusion, fatigue alters landing performance and different fatigue protocols result in different performance changes.

  10. Neuromuscular disorders: genes, genetic counseling and therapeutic trials

    PubMed Central

    Zatz, Mayana; Passos-Bueno, Maria Rita; Vainzof, Mariz

    2016-01-01

    Abstract Neuromuscular disorders (NMD) are a heterogeneous group of genetic conditions, with autosomal dominant, recessive, or X-linked inheritance. They are characterized by progressive muscle degeneration and weakness. Here, we are presenting our major contributions to the field during the past 30 years. We have mapped and identified several novel genes responsible for NMD. Genotype-phenotype correlations studies enhanced our comprehension on the effect of gene mutations on related proteins and their impact on clinical findings. The search for modifier factors allowed the identification of a novel "protective"; variant which may have important implication on therapeutic developments. Molecular diagnosis was introduced in the 1980s and new technologies have been incorporated since then. Next generation sequencing greatly improved our capacity to identify disease-causing mutations with important benefits for research and prevention through genetic counseling of patients' families. Stem cells researches, from and for patients, have been used as tools to study human genetic diseases mechanisms and for therapies development. The clinical effect of preclinical trials in mice and canine models for muscular dystrophies are under investigation. Finally, the integration of our researches and genetic services with our post-graduation program resulted in a significant output of new geneticists, spreading out this expertise to our large country. PMID:27575431

  11. Frontotemporal dementia: a bridge between dementia and neuromuscular disease

    PubMed Central

    Ng, Adeline SL; Rademakers, Rosa; Miller, BL

    2015-01-01

    The concept that frontotemporal dementia (FTD) is a purely “cortical” dementia has largely been refuted by the recognition of its close association with motor neuron disease, and the identification of transactive response DNA-binding protein 43 (TDP-43) as a major pathological substrate underlying both diseases. Genetic findings have transformed this field and revealed connections between disorders that were previous thought clinically unrelated. The discovery of the C9ORF72 locus as responsible for majority of hereditary FTD, ALS and FTD-ALS cases and the understanding that repeat-containing RNA plays a crucial role in pathogenesis of both disorders has paved the way for development of potential biomarkers and therapeutic targets for these devastating diseases. In this review, we summarize the historical aspects leading up to our current understanding of the genetic, clinical and neuropathological overlap between FTD and ALS, and include brief discussions on chronic traumatic encephalopathy (CTE) given its association with TDP-43 pathology, increased dementia risk and reports of ALS in CTE patients. Additionally we describe other genetic associations between dementia and neuromuscular disease, such as inclusion body myositis with Paget’s disease and frontotemporal dementia (IBMPFD). PMID:25557955

  12. Neuromuscular disorders: genes, genetic counseling and therapeutic trials.

    PubMed

    Zatz, Mayana; Passos-Bueno, Maria Rita; Vainzof, Mariz

    2016-01-01

    Neuromuscular disorders (NMD) are a heterogeneous group of genetic conditions, with autosomal dominant, recessive, or X-linked inheritance. They are characterized by progressive muscle degeneration and weakness. Here, we are presenting our major contributions to the field during the past 30 years. We have mapped and identified several novel genes responsible for NMD. Genotype-phenotype correlations studies enhanced our comprehension on the effect of gene mutations on related proteins and their impact on clinical findings. The search for modifier factors allowed the identification of a novel "protective"; variant which may have important implication on therapeutic developments. Molecular diagnosis was introduced in the 1980s and new technologies have been incorporated since then. Next generation sequencing greatly improved our capacity to identify disease-causing mutations with important benefits for research and prevention through genetic counseling of patients' families. Stem cells researches, from and for patients, have been used as tools to study human genetic diseases mechanisms and for therapies development. The clinical effect of preclinical trials in mice and canine models for muscular dystrophies are under investigation. Finally, the integration of our researches and genetic services with our post-graduation program resulted in a significant output of new geneticists, spreading out this expertise to our large country. PMID:27575431

  13. Safe neuromuscular electrical stimulator designed for the elderly.

    PubMed

    Krenn, Matthias; Haller, Michael; Bijak, Manfred; Unger, Ewald; Hofer, Christian; Kern, Helmut; Mayr, Winfried

    2011-03-01

    A stimulator for neuromuscular electrical stimulation (NMES) was designed, especially suiting the requirements of elderly people with reduced cognitive abilities and diminished fine motor skills. The aging of skeletal muscle is characterized by a progressive decline in muscle mass, force, and condition. Muscle training with NMES reduces the degradation process. The discussed system is intended for evoked muscle training of the anterior and posterior thigh. The core of the stimulator is based on a microcontroller with two modular output stages. The system has two charge-balanced biphasic voltage-controlled stimulation channels. Additionally, the evoked myoelectric signal (M-wave) and the myokinematic signal (surface acceleration) are measured. A central controller unit allows using the stimulator as a stand-alone device. To set up the training sequences and to evaluate the compliance data, a personal computer is connected to the stimulator via a universal serial bus. To help elderly people handle the stimulator by themselves, the user interface is kept very simple. For safety reasons, the electrode impedance is monitored during stimulation. A comprehensive compliance management with included measurements of muscle activity and stimulation intensity enables a scientific use of the stimulator in clinical trials. PMID:21401669

  14. [Critical study of radiculomedullary and neuromuscular complications of ankylosing spondylitis].

    PubMed

    Serratrice, G; Acquaviva, P; Pouget, J; Guerra, L

    1987-03-01

    Medullo-radicular and neuro-muscular involvements of ankylosing spondylarthritis, often reported in an analytic fashion in the literature, deserve to be the subject of a critical study. Various neurological manifestations secondary to exceptional atlo-occipital and sometimes axis-atlas subluxations and medullary lesions as well as syndromes of the cauda equina. The medullary lesions have an epidural origin (3 cases in the literature, 2 cases from the authors) or are secondary to a spondylodiscitis (4 cases in the literature) or secondary to both (1 case reported by the authors). As for syndromes of the cauda equina the authors report 3 cases to be added to the 55 published previously. It concerns always old spondylarthritis. The lesions combine posterior diverticula and lesions of the lamina. The treatment is usually ineffective. A special case is represented by forms with trophic disorders. More debatable are the radicular lesions, which, except for intercostal pain, should be linked to local pain. Electromyographic abnormalities are of no significance. Alterations of the paravertebral muscles viewed on the scanner X have, for now, an uncertain significance. Finally, various associations, without significance such as multiple sclerosis, diffuse muscular lesions and the classic spondylotic pseudo-tabes, should be rejected.

  15. [Balters' appliance and its action on the neuromuscular system].

    PubMed

    Travesi Gomez, J

    1992-01-01

    Bionator created by BALTERS comes directly from activator but is smaller allowing its use during day and night to achieve mainly: lip closure, tongue in contact with soft palate, make oral area bigger improving its functionality, get a better maxillary relationship making mandible longer and improve tongue position. The principle that a new neuromuscular pattern conducted by appliance drives to development of a new morphologic pattern. Its activity on neuromusculature is neither well documented nor studied. Actually it is admitted that craniomandibular muscles contraction depends on neural pattern of this muscles during movement. This pattern is modified by continuous sensorial feed-back coming from dentition, T.M.J., and muscular and tendinal length and strength receptors. Clinical studies on mandibular advancement, show that occlusion alteration in sagittal mandibular reposition drives to spontaneous activity changes in muscles and to changes in electromyographic rest of certain muscles like the temporal. In some cases it is founded an increase in molar bite due to anterior mandibular reposition force. Clinical studies on mandibular advancement show changes on mandibular muscles spontaneous activity and possibility of modifications of E.M.G. rest level of temporalis. In some cases an increasing of bite force on first molars is founded. Electromyographic changes appear in children early, and produce a new functional position that changes morphology. Feed-back information comes from periodontal and muscular receptors. Patients treated show lip closure without strength, better tongue positioning and swallowing, and lower tension on suprahyoid muscles.

  16. Development of neuromuscular organization in the ctenophore Pleurobrachia bachei.

    PubMed

    Norekian, Tigran P; Moroz, Leonid L

    2016-01-01

    The phylogenetic position of the phylum Ctenophora and the nature of ctenphore nervous systems are highly debated topics in modern evolutionary biology. However, very little is known about the organization of ctenophore neural and muscular systems, and virtually nothing has been reported about their embryogenesis. Here we have characterized the neural and muscular development of the sea gooseberry, Pleurobrachia bachei, starting from the cleavage stages to posthatching larvae. Scanning electron microscopy and immunochemistry were used to describe the formation of the embryonic mouth, tentacles, combs, aboral organ, and putative sensory cells. The muscles started their specification at the end of the first day of Pleurobrachia development. In contrast, neurons appeared 2 days after myogenesis, just before the hatching of fully formed cydippid larvae. The first tubulin-immunoreactive neurons, a small group of four to six cells with neuronal processes, was initially recognized at the aboral pole during the third day of development. Surprisingly, this observed neurogenesis occurred after the emergence of distinct behavioral patterns in the embryos. Thus, the embryonic behavior associated with comb cilia beatings and initial muscle organization does not require morphologically defined neurons and their elongated neurites. This study provides the first description of neuromuscular development in the enigmatic ctenophores and establishes the foundation for future research using emerging genomic tools and resources.

  17. Active zones of mammalian neuromuscular junctions: formation, density, and aging

    PubMed Central

    Nishimune, Hiroshi

    2012-01-01

    Presynaptic active zones are synaptic vesicle release sites that playessential roles in the function and pathology of mammalian neuromuscular junctions (NMJs). The molecular mechanisms of active zone organization utilize presynaptic voltage-dependent calcium channels (VDCCs) in NMJs as scaffolding proteins. VDCCs interact extracellularly with the muscle-derived synapse organizer, laminin β2, and interact intracellularly with active zone-specific proteins, such as Bassoon, CAST/Erc2/ELKS2alpha, ELKS, Piccolo, and RIMs. These molecular mechanisms are supported by studies in P/Q- and N-type VDCCs double-knockout mice, and they are consistent with the pathological conditions of Lambert-Eaton myasthenic syndrome and Pierson syndrome, which are caused by autoantibodies against VDCCs or by a laminin β2 mutation. During normal postnatal maturation, NMJs maintain the density of active zones, while NMJs triple their size. However, active zones become impaired during aging. Propitiously, muscle exercise ameliorates the active zone impairment in aged NMJs, which suggests the potential for therapeutic strategies. PMID:23252894

  18. Degeneration of Neuromuscular Junction in Age and Dystrophy

    PubMed Central

    Rudolf, Rüdiger; Khan, Muzamil Majid; Labeit, Siegfried; Deschenes, Michael R.

    2014-01-01

    Functional denervation is a hallmark of aging sarcopenia as well as of muscular dystrophy. It is thought to be a major factor reducing skeletal muscle mass, particularly in the case of sarcopenia. Neuromuscular junctions (NMJs) serve as the interface between the nervous and skeletal muscular systems, and thus they may receive pathophysiological input of both pre- and post-synaptic origin. Consequently, NMJs are good indicators of motor health on a systemic level. Indeed, upon sarcopenia and dystrophy, NMJs morphologically deteriorate and exhibit altered characteristics of primary signaling molecules, such as nicotinic acetylcholine receptor and agrin. Since a remarkable reversibility of these changes can be observed by exercise, there is significant interest in understanding the molecular mechanisms underlying synaptic deterioration upon aging and dystrophy and how synapses are reset by the aforementioned treatments. Here, we review the literature that describes the phenomena observed at the NMJ in sarcopenic and dystrophic muscle as well as to how these alterations can be reversed and to what extent. In a second part, the current information about molecular machineries underlying these processes is reported. PMID:24904412

  19. Level of independence of motor unit properties from neuromuscular activity.

    PubMed

    Pierotti, D J; Roy, R R; Hodgson, J A; Edgerton, V R

    1994-11-01

    Neuromuscular activity was eliminated in the tibialis anterior muscle of adult cats for 6 months by spinal isolation (SI), i.e., complete spinal cord transections at T-12-13 and at L-7-S-1, plus bilateral dorsal rhizotomy between the two transection sites. One motor unit from each muscle was isolated using ventral root teasing procedures and physiologically tested. The fibers belonging to each motor unit were visualized in PAS-stained sections by the loss of glycogen following prolonged repetitive stimulation. Qualitatively, the normal enzymatic interrelationships among fibers identified by myosin heavy chain composition were unchanged by SI. Generally, each motor unit from SI cats were of a single myosin immunohistochemical type. The same physiological motor unit types that typify control muscles were found in SI cats. In SI compared to control cats, there was approximately a 10% increase in the number of muscle fibers expressing fast myosin. Mean fiber activity levels of ATPase and SDH for a given fiber type (based on MHC antibody reactions) decreased by approximately 10% and 25%, whereas GPD activity increased approximately 35%. It is concluded that differential levels or patterns of activity are not essential to maintain the range of histochemical and physiological motor unit types found in the tibialis anterior of normal adult cats.

  20. Applications of shape memory alloys for neurology and neuromuscular rehabilitation.

    PubMed

    Pittaccio, Simone; Garavaglia, Lorenzo; Ceriotti, Carlo; Passaretti, Francesca

    2015-01-01

    Shape memory alloys (SMAs) are a very promising class of metallic materials that display interesting nonlinear properties, such as pseudoelasticity (PE), shape memory effect (SME) and damping capacity, due to high mechanical hysteresis and internal friction. Our group has applied SMA in the field of neuromuscular rehabilitation, designing some new devices based on the mentioned SMA properties: in particular, a new type of orthosis for spastic limb repositioning, which allows residual voluntary movement of the impaired limb and has no predetermined final target position, but follows and supports muscular elongation in a dynamic and compliant way. Considering patients in the sub-acute phase after a neurological lesion, and possibly bedridden, the paper presents a mobiliser for the ankle joint, which is designed exploiting the SME to provide passive exercise to the paretic lower limb. Two different SMA-based applications in the field of neuroscience are then presented, a guide and a limb mobiliser specially designed to be compatible with diagnostic instrumentations that impose rigid constraints in terms of electromagnetic compatibility and noise distortion. Finally, the paper discusses possible uses of these materials in the treatment of movement disorders, such as dystonia or hyperkinesia, where their dynamic characteristics can be advantageous.

  1. Pseudoephedrine and circadian rhythm interaction on neuromuscular performance.

    PubMed

    Pallarés, J G; López-Samanes, Á; Fernández-Elías, V E; Aguado-Jiménez, R; Ortega, J F; Gómez, C; Ventura, R; Segura, J; Mora-Rodríguez, R

    2015-12-01

    This study analyzed the effects of pseudoephedrine (PSE) provided at different time of day on neuromuscular performance, side effects, and violation of the current doping cut-off threshold [World Anti-Doping Agency (WADA)]. Nine resistance-trained males carried out bench press and full squat exercises against four incremental loads (25%, 50%, 75%, and 90% one repetition maximum [1RM]), in a randomized, double-blind, cross-over design. Participants ingested either 180 mg of PSE (supra-therapeutic dose) or placebo in the morning (7:00 h; AM(PLAC) and AM(PSE)) and in the afternoon (17:00 h; PM(PLAC) and PM(PSE)). PSE enhanced muscle contraction velocity against 25% and 50% 1RM loads, only when it was ingested in the mornings, and only in the full squat exercise (4.4-8.7%; P < 0.05). PSE ingestion raised urine and plasma PSE concentrations (P < 0.05) regardless of time of day; however, cathine only increased in the urine samples. PSE ingestion resulted in positive tests occurring in 11% of samples, and it rose some adverse side effects such us tachycardia and heart palpitations. Ingestion of a single dose of 180 mg of PSE results in enhanced lower body muscle contraction velocity against low and moderate loads only in the mornings. These mild performance improvements are accompanied by undesirable side effects and an 11% risk of surpassing the doping threshold.

  2. Neuromuscular strategies contributing to faster multidirectional agility performance.

    PubMed

    Spiteri, Tania; Newton, Robert U; Nimphius, Sophia

    2015-08-01

    The aim of this study was to first determine differences in neuromuscular strategy between a faster and slower agility performance, and second compare differences in muscle activation strategy employed when performing two closely executed agility movements. Participants recruited from an elite female basketball team completed an ultrasound to determine quadriceps muscle-cross sectional area; reactive isometric mid-thigh pull to determine the rate of muscle activation, rate of force development, pre-motor time and motor time; and multidirectional agility tests completing two directional changes in response to a visual stimulus. Peak and average relative muscle activation of the rectus femoris, vastus medialis, vastus lateralis, biceps femoris, semitendinosus and gastrocnemius were measured 100ms prior to heel strike (pre-heel strike) and across stance phase for both directional changes. Faster agility performance was characterized by greater pre-heel strike muscle activity and greater anterior muscle activation during stance phase resulting in greater hip and knee extension increasing propulsive impulse. Differences between directional changes appear to result from processing speed, where a greater delay in refractory times during the second directional change resulted in greater anterior muscle activation, decelerating the body while movement direction was determined.

  3. Influenza virus subpopulations: interferon induction-suppressing particles require expression of NS1 and act globally in cells; UV irradiation of interferon-inducing particles blocks global shut-off and enhances interferon production.

    PubMed

    Malinoski, Christopher P; Marcus, Philip I

    2013-02-01

    Influenza virus populations contain several subpopulations of noninfectious biologically active particles that are measured by the unique phenotypes they express. Two of these subpopulations were studied: (1) interferon (IFN)-inducing particles (IFP) and (2) IFN induction-suppressing particles (ISP). ISP are dominant in cells coinfected with one or more IFP; they completely suppress IFN production in cells otherwise programmed to induce it. Influenza virus ISP were shown to act in host cells in a nonspecific and global manner, suppressing IFN induction independent of the family of viruses serving as IFN inducers. ISP must be present within the first 3 h of coinfection with IFP to be maximally effective; by 7 hpi IFN induction/production is refractory to the action of superinfecting ISP. UV target and thermal inactivation analyses revealed that ISP activity was dependent solely on the expression of the NS gene. Low doses of UV radiation enhanced by ∼10-fold the already high IFN-inducing capacity of a virus that expressed truncated NS1. There was no change in the number of IFP, implying that the production of IFN/cell had increased. We postulated that preventing degradation of cellular RNA pol II by viral polymerase prolonged the transcription of cellular mRNA, including IFN mRNA, to enhance the IFN-inducing capacity of the cell without any increase in the number of IFP. These studies point to the dueling roles of IFP and ISP in modulating IFN induction/production, the former activity being critical to the efficacy of live attenuated influenza vaccines.

  4. Corrective Neuromuscular Approach to the Treatment of Iliotibial Band Friction Syndrome: A Case Report

    PubMed Central

    Pettitt, Robert; Dolski, Angela

    2000-01-01

    Objective: To describe the evaluation and treatment process for inappropriate functional patterns of neuromuscular activity within the scope of an iliotibial band friction syndrome protocol. Background: Runners with iliotibial band friction syndrome are frequently fitted with orthotic devices to restrict excessive midfoot or rearfoot, or both, motions during the stance phase. These devices may fail to yield favorable results when underlying neuromuscular factors are associated with functional iliotibial band tightening. Differential Diagnosis: Distal biceps femoris tendinitis, popliteal tendinitis, lateral meniscus lesion. Treatment: The athlete's physical examination revealed several patterns of inappropriate neuromuscular activity attributed partly to the prolonged daily wear of beach-type sandals. Modifications of casual footwear and a temporary reduction in training volume were recommended initially to prevent exacerbation of the athlete's condition. Stretching, massage, and soft tissue mobilization were administered in accordance with the athlete's specific needs. The protocol included progressions of nonweightbearing and weightbearing therapeutic exercises. Neuromuscular electric stimulation was incorporated into the protocol to re-educate the role of the first ray within the stance phase of the athlete's walking gait. Uniqueness: Upon stationary examination, this athlete presented with normal lumbar and lower extremity postures. Gait analysis, however, revealed inappropriate dorsiflexion of the great toe during ambulation. Further, the athlete's performances on a series of tests to assess neuromuscular function were substandard. This athlete's response to previous treatment and unique physical findings required a corrective neuromuscular approach that deviates from iliotibial band friction syndrome protocols advocating the use of orthotics. Conclusions: While the role of any single treatment in the athlete's recovery remains unknown, it seems that a

  5. Neutralization of the neuromuscular inhibition of venom and taipoxin from the taipan (Oxyuranus scutellatus) by F(ab')2 and whole IgG antivenoms.

    PubMed

    Herrera, María; de Cássia de O Collaço, Rita; Villalta, Mauren; Segura, Álvaro; Vargas, Mariángela; Wright, Christine E; Paiva, Owen K; Matainaho, Teatulohi; Jensen, Simon D; León, Guillermo; Williams, David J; Rodrigues-Simioni, Léa; Gutiérrez, José María

    2016-01-22

    The neuromuscular junction activity of Oxyuranus scutellatus venom and its presynaptic neurotoxin, taipoxin, and their neutralization by two antivenoms were examined in mouse phrenic nerve-diaphragm preparations. The action of taipoxin was also studied at 21°C. The efficacy of the antivenoms was also assessed in an in vivo mouse model. Both antivenoms were effective in neutralizing the neuromuscular blocking activity in preincubation-type experiments. In experiments involving independent addition of venom and antivenoms, neutralization depended on the time interval between venom addition and antivenom application. When taipoxin was incubated for 5, 10 or 20min at 21°C, and antivenom added and temperature increased to 37°C, neutralization was achieved only when the toxin was incubated for 5 or 10min. The neutralization by the two antivenoms in an in vivo model showed that both whole IgG and F(ab')2 antivenoms were effective in neutralizing lethality. Our findings highlight the very rapid action of taipan venom at the nerve terminal, and the poor capacity of antivenoms to revert neurotoxicity as the time interval between venom or taipoxin application and antivenom addition increased. Additionally the disparity between molecular masses of the active substances of the two antivenoms did not result in differences in neutralization.

  6. Neutralization of the neuromuscular inhibition of venom and taipoxin from the taipan (Oxyuranus scutellatus) by F(ab')2 and whole IgG antivenoms.

    PubMed

    Herrera, María; de Cássia de O Collaço, Rita; Villalta, Mauren; Segura, Álvaro; Vargas, Mariángela; Wright, Christine E; Paiva, Owen K; Matainaho, Teatulohi; Jensen, Simon D; León, Guillermo; Williams, David J; Rodrigues-Simioni, Léa; Gutiérrez, José María

    2016-01-22

    The neuromuscular junction activity of Oxyuranus scutellatus venom and its presynaptic neurotoxin, taipoxin, and their neutralization by two antivenoms were examined in mouse phrenic nerve-diaphragm preparations. The action of taipoxin was also studied at 21°C. The efficacy of the antivenoms was also assessed in an in vivo mouse model. Both antivenoms were effective in neutralizing the neuromuscular blocking activity in preincubation-type experiments. In experiments involving independent addition of venom and antivenoms, neutralization depended on the time interval between venom addition and antivenom application. When taipoxin was incubated for 5, 10 or 20min at 21°C, and antivenom added and temperature increased to 37°C, neutralization was achieved only when the toxin was incubated for 5 or 10min. The neutralization by the two antivenoms in an in vivo model showed that both whole IgG and F(ab')2 antivenoms were effective in neutralizing lethality. Our findings highlight the very rapid action of taipan venom at the nerve terminal, and the poor capacity of antivenoms to revert neurotoxicity as the time interval between venom or taipoxin application and antivenom addition increased. Additionally the disparity between molecular masses of the active substances of the two antivenoms did not result in differences in neutralization. PMID:26621539

  7. Presynaptic neuromuscular action of a methanolic extract from the venom of Rhinella schneideri toad

    PubMed Central

    2014-01-01

    Background Rhinella schneideri, previously known as Bufo paracnemis, is a common toad in many regions of Brazil. Its venom exerts important cardiovascular effects on humans and other animals. Although this toad venom has been the subject of intense investigations, little is known about its neuromuscular activity. Methods The neurotoxicity of a methanolic extract of R. schneideri venom was tested on mouse phrenic nerve-diaphragm (PND) preparations mounted for conventional twitch tension recording – in response to indirect stimulation – and for electrophysiological measurements. Results Venom extract (50 μg/mL) increased the muscle twitch tension in PND preparations but did not significantly alter the resting membrane potential values. Electrophysiological evaluations showed that the extract (50 μg/mL) significantly augmented the frequency of miniature end-plate potential (from 38 ± 3.5 to 88 ± 15 after 60 minutes; n = 5; p < 0.05) and quantal content (from 128 ± 13 to 272 ± 34 after five minutes; n = 5; p < 0.05). Pretreatment with ouabain (1 μg/mL) for five minutes prevented the increase in quantal content (117 ± 18 and 154 ± 33 after five and 60 minutes, respectively). Conclusion These results indicate that the methanolic extract of R. schneideri venom acts primarily presynaptically to enhance neurotransmitter release in mouse phrenic-diaphragm preparations. PMID:25024696

  8. Juggling Act

    ERIC Educational Resources Information Center

    Rudalevige, Andrew

    2009-01-01

    Two education bills from George W. Bush's first term are long overdue for reauthorization. One, of course, is the No Child Left Behind Act (NCLB), passed in late 2001. The other is the Education Sciences Reform Act (ESRA), which in November 2002 replaced the Office of Educational Research and Improvement (OERI) with a new Institute of Education…

  9. Congenital complete atrioventricular block.

    PubMed Central

    Kertesz, N J; Fenrich, A L; Friedman, R A

    1997-01-01

    Congenital complete atrioventricular block is found in 1 of 22,000 live births. Over time, it has become apparent that these patients represent not a single distinct disease process, but several processes with the common manifestation of atrioventricular block. The evaluation of these patients to determine their risk of sudden death and need for pacing is not well defined. Images PMID:9456483

  10. High Relief Block Printing.

    ERIC Educational Resources Information Center

    Foster, Michael

    1989-01-01

    Explains a method of block printing using styrofoam shapes to make high relief. Describes the creation of the block design as well as the actual printing process. Uses a range of paper types for printing so children can see the results of using different media. (LS)

  11. Surviving Block Scheduling.

    ERIC Educational Resources Information Center

    Haley, Marjorie

    A discussion of block scheduling for second language instruction looks at the advantages and disadvantages and offers some suggestions for classroom management and course organization. It is argued that block scheduling may offer a potential solution to large classes, insufficient time for labs, too little individualized instruction; few…

  12. Thermally actuated wedge block

    DOEpatents

    Queen, Jr., Charles C.

    1980-01-01

    This invention relates to an automatically-operating wedge block for maintaining intimate structural contact over wide temperature ranges, including cryogenic use. The wedging action depends on the relative thermal expansion of two materials having very different coefficients of thermal expansion. The wedge block expands in thickness when cooled to cryogenic temperatures and contracts in thickness when returned to room temperature.

  13. Targeting of the ETS Factor Gabpα Disrupts Neuromuscular Junction Synaptic Function▿ §

    PubMed Central

    O'Leary, Debra A.; Noakes, Peter G.; Lavidis, Nick A.; Kola, Ismail; Hertzog, Paul J.; Ristevski, Sika

    2007-01-01

    The GA-binding protein (GABP) transcription factor has been shown in vitro to regulate the expression of the neuromuscular proteins utrophin, acetylcholine esterase, and acetylcholine receptor subunits δ and ɛ through the N-box promoter motif (5′-CCGGAA-3′), but its in vivo function remains unknown. A single point mutation within the N-box of the gene encoding the acetylcholine receptor ɛ subunit has been identified in several patients suffering from postsynaptic congenital myasthenic syndrome, implicating the GA-binding protein in neuromuscular function and disease. Since conventional gene targeting results in an embryonic-lethal phenotype, we used conditional targeting to investigate the role of GABPα in neuromuscular junction and skeletal muscle development. The diaphragm and soleus muscles from mutant mice display alterations in morphology and distribution of acetylcholine receptor clusters at the neuromuscular junction and neurotransmission properties consistent with reduced receptor function. Furthermore, we confirmed decreased expression of the acetylcholine receptor ɛ subunit and increased expression of the γ subunit in skeletal muscle tissues. Therefore, the GABP transcription factor aids in the structural formation and function of neuromuscular junctions by regulating the expression of postsynaptic genes. PMID:17325042

  14. A Dutch guideline for the treatment of scoliosis in neuromuscular disorders

    PubMed Central

    Mullender, MG; Blom, NA; De Kleuver, M; Fock, JM; Hitters, WMGC; Horemans, AMC; Kalkman, CJ; Pruijs, JEH; Timmer, RR; Titarsolej, PJ; Van Haasteren, NC; Jager, MJ Van Tol-de; Van Vught, AJ; Van Royen, BJ

    2008-01-01

    Background Children with neuromuscular disorders with a progressive muscle weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy frequently develop a progressive scoliosis. A severe scoliosis compromises respiratory function and makes sitting more difficult. Spinal surgery is considered the primary treatment option for correcting severe scoliosis in neuromuscular disorders. Surgery in this population requires a multidisciplinary approach, careful planning, dedicated surgical procedures, and specialized after care. Methods The guideline is based on scientific evidence and expert opinions. A multidisciplinary working group representing experts from all relevant specialties performed the research. A literature search was conducted to collect scientific evidence in answer to specific questions posed by the working group. Literature was classified according to the level of evidence. Results For most aspects of the treatment scientific evidence is scarce and only low level cohort studies were found. Nevertheless, a high degree of consensus was reached about the management of patients with scoliosis in neuromuscular disorders. This was translated into a set of recommendations, which are now officially accepted as a general guideline in the Netherlands. Conclusion In order to optimize the treatment for scoliosis in neuromuscular disorders a Dutch guideline has been composed. This evidence-based, multidisciplinary guideline addresses conservative treatment, the preoperative, perioperative, and postoperative care of scoliosis in neuromuscular disorders. PMID:18822133

  15. Gait and Neuromuscular Asymmetries after Acute ACL Rupture

    PubMed Central

    Gardinier, Emily S.; Manal, Kurt; Buchanan, Thomas S.; Snyder-Mackler, Lynn

    2012-01-01

    The decreased internal knee extensor moment is a significant gait asymmetry among patients with anterior cruciate ligament (ACL) deficiency, yet the muscular strategy driving this altered moment for the injured limb is unclear. Purpose To determine whether patients with ACL deficiency and characteristic knee instability would demonstrate normal extensor and increased flexor muscle force to generate a decreased internal extensor moment (i.e. employ a hamstring facilitation strategy). Methods Gait analysis was performed on 31 athletes with acute ACL rupture who exhibited characteristic knee instability after injury. Peak internal knee extensor moment was calculated using inverse dynamics and muscle forces were estimated using an EMG-driven modeling approach. Comparisons were made between the injured and contralateral limbs. Results As expected, patients demonstrated decreased peak knee flexion (p=0.028) and internal knee extensor moment (p=0.0004) for their injured limb, but exhibited neither an isolated decrease in extensor force (quadriceps avoidance), nor an isolated increase in flexor force (hamstring facilitation) at peak knee moment. Instead, they exhibited decreased muscle force from both flexor (p=0.0001) and extensor (p=0.0103) groups. This strategy of decreased muscle force may be explained in part by muscle weakness which frequently accompanies ACL injury, or by apprehension, low confidence and fear of further injury. Conclusions This is the first study to estimate muscle forces in the ACL-deficient knee using an EMG-driven approach. These results affirm the existence of neuromuscular asymmetries in the individuals with ACL deficiency and characteristic knee instability. PMID:22330021

  16. Kinetics of neuromuscular changes during low-frequency electrical stimulation.

    PubMed

    Papaiordanidou, Maria; Guiraud, David; Varray, Alain

    2010-01-01

    The purpose of the study was to examine the time course of neuromuscular fatigue components during a low-frequency electrostimulation (ES) session. Three bouts of 17 trains of stimulation at 30 HZ (4 s on, 6 s off) were used to electrically induce fatigue in the plantar flexor muscles. Before and after every 17-train bout, torque, electromyographic activity [expressed as root mean square (RMS) and median frequency (MF) values], evoked potentials (M-wave and H-reflex), and the level of voluntary activation (LOA, using twitch interpolation technique) were assessed. Torque during maximal voluntary contraction decreased significantly from the very first stimulation bout (-6.6 +/- 1.11%, P < 0.001) and throughout the session (-10.32 +/- 1.68% and -11.53 +/- 1.27%, for the second and third bouts, respectively). The LOA and RMS/Mmax values were significantly decreased during the ES session (-2.9 +/- 1.07% and -17.5 +/- 6.14%, P < 0.01 and P< 0.001, respectively, at the end of the protocol), while MF showed no changes. The Hmax/Mmax ratio and Mmax were not significantly modified during the session. All twitch parameters were significantly potentiated after the first bout and throughout the session (P < 0.001). The maximal torque decrease was evident from the early phase of a low-frequency ES protocol, with no concomitant inhibition of motoneuron excitability or depression of muscle contractile properties. These results are consistent with an early failure of the central drive to the muscle. PMID:19882645

  17. Wnt4 Participates in the Formation of Vertebrate Neuromuscular Junction

    PubMed Central

    Strochlic, Laure; Falk, Julien; Goillot, Evelyne; Sigoillot, Séverine; Bourgeois, Francine; Delers, Perrine; Rouvière, Jérôme; Swain, Amanda; Castellani, Valérie; Schaeffer, Laurent; Legay, Claire

    2012-01-01

    Neuromuscular junction (NMJ) formation requires the highly coordinated communication of several reciprocal signaling processes between motoneurons and their muscle targets. Identification of the early, spatially restricted cues in target recognition at the NMJ is still poorly documented, especially in mammals. Wnt signaling is one of the key pathways regulating synaptic connectivity. Here, we report that Wnt4 contributes to the formation of vertebrate NMJ in vivo. Results from a microarray screen and quantitative RT-PCR demonstrate that Wnt4 expression is regulated during muscle cell differentiation in vitro and muscle development in vivo, being highly expressed when the first synaptic contacts are formed and subsequently downregulated. Analysis of the mouse Wnt4−/− NMJ phenotype reveals profound innervation defects including motor axons overgrowing and bypassing AChR aggregates with 30% of AChR clusters being unapposed by nerve terminals. In addition, loss of Wnt4 function results in a 35% decrease of the number of prepatterned AChR clusters while Wnt4 overexpression in cultured myotubes increases the number of AChR clusters demonstrating that Wnt4 directly affects postsynaptic differentiation. In contrast, muscle structure and the localization of several synaptic proteins including acetylcholinesterase, MuSK and rapsyn are not perturbed in the Wnt4 mutant. Finally, we identify MuSK as a Wnt4 receptor. Wnt4 not only interacts with MuSK ectodomain but also mediates MuSK activation. Taken together our data reveal a new role for Wnt4 in mammalian NMJ formation that could be mediated by MuSK, a key receptor in synaptogenesis. PMID:22253844

  18. Neuromuscular consequences of an extreme mountain ultra-marathon.

    PubMed

    Millet, Guillaume Y; Tomazin, Katja; Verges, Samuel; Vincent, Christopher; Bonnefoy, Régis; Boisson, Renée-Claude; Gergelé, Laurent; Féasson, Léonard; Martin, Vincent

    2011-01-01

    We investigated the physiological consequences of one of the most extreme exercises realized by humans in race conditions: a 166-km mountain ultra-marathon (MUM) with 9500 m of positive and negative elevation change. For this purpose, (i) the fatigue induced by the MUM and (ii) the recovery processes over two weeks were assessed. Evaluation of neuromuscular function (NMF) and blood markers of muscle damage and inflammation were performed before and immediately following (n = 22), and 2, 5, 9 and 16 days after the MUM (n = 11) in experienced ultra-marathon runners. Large maximal voluntary contraction decreases occurred after MUM (-35% [95% CI: -28 to -42%] and -39% [95% CI: -32 to -46%] for KE and PF, respectively), with alteration of maximal voluntary activation, mainly for KE (-19% [95% CI: -7 to -32%]). Significant modifications in markers of muscle damage and inflammation were observed after the MUM as suggested by the large changes in creatine kinase (from 144 ± 94 to 13,633 ± 12,626 UI L(-1)), myoglobin (from 32 ± 22 to 1,432 ± 1,209 µg L(-1)), and C-Reactive Protein (from <2.0 to 37.7 ± 26.5 mg L(-1)). Moderate to large reductions in maximal compound muscle action potential amplitude, high-frequency doublet force, and low frequency fatigue (index of excitation-contraction coupling alteration) were also observed for both muscle groups. Sixteen days after MUM, NMF had returned to initial values, with most of the recovery process occurring within 9 days of the race. These findings suggest that the large alterations in NMF after an ultra-marathon race are multi-factorial, including failure of excitation-contraction coupling, which has never been described after prolonged running. It is also concluded that as early as two weeks after such an extreme running exercise, maximal force capacities have returned to baseline.

  19. Effects of hindlimb unloading on neuromuscular development of neonatal rats

    NASA Technical Reports Server (NTRS)

    Huckstorf, B. L.; Slocum, G. R.; Bain, J. L.; Reiser, P. M.; Sedlak, F. R.; Wong-Riley, M. T.; Riley, D. A.

    2000-01-01

    We hypothesized that hindlimb suspension unloading of 8-day-old neonatal rats would disrupt the normal development of muscle fiber types and the motor innervation of the antigravity (weightbearing) soleus muscles but not extensor digitorum longus (EDL) muscles. Five rats were suspended 4.5 h and returned 1.5 h to the dam for nursing on a 24 h cycle for 9 days. To control for isolation from the dam, the remaining five littermates were removed on the same schedule but not suspended. Another litter of 10 rats housed in the same room provided a vivarium control. Fibers were typed by myofibrillar ATPase histochemistry and immunostaining for embryonic, slow, fast IIA and fast IIB isomyosins. The percentage of multiple innervation and the complexity of singly-innervated motor terminal endings were assessed in silver/cholinesterase stained sections. Unique to the soleus, unloading accelerated production of fast IIA myosin, delayed expression of slow myosin and retarded increases in standardized muscle weight and fiber size. Loss of multiple innervation was not delayed. However, fewer than normal motor nerve endings achieved complexity. Suspended rats continued unloaded hindlimb movements. These findings suggest that motor neurons resolve multiple innervation through nerve impulse activity, whereas the postsynaptic element (muscle fiber) controls endplate size, which regulates motor terminal arborization. Unexpectedly, in the EDL of unloaded rats, transition from embryonic to fast myosin expression was retarded. Suspension-related foot drop, which stretches and chronically loads EDL, may have prevented fast fiber differentiation. These results demonstrate that neuromuscular development of both weightbearing and non-weightbearing muscles in rats is dependent upon and modulated by hindlimb loading.

  20. ACT Test

    MedlinePlus

    ... this page helpful? Also known as: ACT; Activated Coagulation Time Formal name: Activated Clotting Time Related tests: ... in the blood called platelets and proteins called coagulation factors are activated in a sequence of steps ...

  1. Acting Atoms.

    ERIC Educational Resources Information Center

    Farin, Susan Archie

    1997-01-01

    Describes a fun game in which students act as electrons, protons, and neutrons. This activity is designed to help students develop a concrete understanding of the abstract concept of atomic structure. (DKM)

  2. Characterization of blocked isocyanates

    NASA Astrophysics Data System (ADS)

    Mirčeva, A.; Janežič, M.; Žigon, M.; Malavašič, T.

    1992-03-01

    An ionomer crosslinker on the basis of partly blocked hexamethylene isocyanurate was synthesized and characterized by FTIR and NMR spectroscopy and by gel permeation chromatography. To determine the selectivity of the blocking reaction. model compounds were also prepared. Deblocking and curing courses were studied by FTIR thermal methods. The selectivity of the blocking reaction was found to be poor and therefore the obtained ionomer crosslinker consisted of different monomer and oligomer components. Deblocking and curing were highly temperature dependent. Curing was more efficient in one-pack systems consisting of the ionomer crosslinker and of an OH groups rich ionomer polyurethane resin.

  3. Local identifiability and sensitivity analysis of neuromuscular blockade and depth of hypnosis models.

    PubMed

    Silva, M M; Lemos, J M; Coito, A; Costa, B A; Wigren, T; Mendonça, T

    2014-01-01

    This paper addresses the local identifiability and sensitivity properties of two classes of Wiener models for the neuromuscular blockade and depth of hypnosis, when drug dose profiles like the ones commonly administered in the clinical practice are used as model inputs. The local parameter identifiability was assessed based on the singular value decomposition of the normalized sensitivity matrix. For the given input signal excitation, the results show an over-parameterization of the standard pharmacokinetic/pharmacodynamic models. The same identifiability assessment was performed on recently proposed minimally parameterized parsimonious models for both the neuromuscular blockade and the depth of hypnosis. The results show that the majority of the model parameters are identifiable from the available input-output data. This indicates that any identification strategy based on the minimally parameterized parsimonious Wiener models for the neuromuscular blockade and for the depth of hypnosis is likely to be more successful than if standard models are used.

  4. Analgesia, sedation, and neuromuscular blockade during targeted temperature management after cardiac arrest.

    PubMed

    Riker, Richard R; Gagnon, David J; May, Teresa; Seder, David B; Fraser, Gilles L

    2015-12-01

    The approach to sedation, analgesia, and neuromuscular blockade during targeted temperature management (TTM) remains largely unstudied, forcing clinicians to adapt previous research from other patient environments. During TTM, very little data guide drug selection, doses, and specific therapeutic goals. Sedation should be deep enough to prevent awareness during neuromuscular blockade, but titration is complex as metabolism and clearance are delayed for almost all drugs during hypothermia. Deeper sedation is associated with prolonged intensive care unit (ICU) and ventilator therapy, increased delirium and infection, and delayed wakening which can confound early critical neurological assessments, potentially resulting in erroneous prognostication and inappropriate withdrawal of life support. We review the potential therapeutic goals for sedation, analgesia, and neuromuscular blockade during TTM; the adverse events associated with that treatment; data suggesting that TTM and organ dysfunction impair drug metabolism; and controversies and potential benefits of specific monitoring. We also highlight the areas needing better research to guide our therapy. PMID:26670815

  5. Neuromuscular electrical stimulation in critically ill patients in the intensive care unit: a systematic review

    PubMed Central

    Ferreira, Lucas Lima; Vanderlei, Luiz Carlos Marques; Valenti, Vitor Engrácia

    2014-01-01

    Objective To analyze the outcomes enabled by the neuromuscular electric stimulation in critically ill patients in intensive care unit assisted. Methods A systematic review of the literature by means of clinical trials published between 2002 and 2012 in the databases LILACS, SciELO, MEDLINE and PEDro using the descriptors “intensive care unit”, “physical therapy”, “physiotherapy”, “electric stimulation” and “randomized controlled trials”. Results We included four trials. The sample size varied between 8 to 33 individuals of both genders, with ages ranging between 52 and 79 years, undergoing invasive mechanical ventilation. Of the articles analyzed, three showed significant benefits of neuromuscular electrical stimulation in critically ill patients, such as improvement in peripheral muscle strength, exercise capacity, functionality, or loss of thickness of the muscle layer. Conclusion The application of neuromuscular electrical stimulation promotes a beneficial response in critically patients in intensive care. PMID:25295458

  6. Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease

    PubMed Central

    Khan, Muzamil Majid; Lustrino, Danilo; Silveira, Willian A.; Wild, Franziska; Straka, Tatjana; Issop, Yasmin; O’Connor, Emily; Cox, Dan; Reischl, Markus; Marquardt, Till; Labeit, Dittmar; Labeit, Siegfried; Benoit, Evelyne; Molgó, Jordi; Lochmüller, Hanns; Witzemann, Veit; Kettelhut, Isis C.; Navegantes, Luiz C. C.; Pozzan, Tullio; Rudolf, Rüdiger

    2016-01-01

    The distribution and function of sympathetic innervation in skeletal muscle have largely remained elusive. Here we demonstrate that sympathetic neurons make close contact with neuromuscular junctions and form a network in skeletal muscle that may functionally couple different targets including blood vessels, motor neurons, and muscle fibers. Direct stimulation of sympathetic neurons led to activation of muscle postsynaptic β2-adrenoreceptor (ADRB2), cAMP production, and import of the transcriptional coactivator peroxisome proliferator-activated receptor γ-coactivator 1α (PPARGC1A) into myonuclei. Electrophysiological and morphological deficits of neuromuscular junctions upon sympathectomy and in myasthenic mice were rescued by sympathicomimetic treatment. In conclusion, this study identifies the neuromuscular junction as a target of the sympathetic nervous system and shows that sympathetic input is crucial for synapse maintenance and function. PMID:26733679

  7. Bone mineral density evaluation among patients with neuromuscular scoliosis secondary to cerebral palsy☆

    PubMed Central

    Rezende, Rodrigo; Cardoso, Igor Machado; Leonel, Rayana Bomfim; Perim, Larissa Grobério Lopes; Oliveira, Tarcísio Guimarães Silva; Jacob Júnior, Charbel; Júnior, José Lucas Batista; Lourenço, Rafael Burgomeister

    2014-01-01

    Objective To evaluate bone mineral density among patients with neuromuscular scoliosis secondary to quadriplegic cerebral palsy. Methods This was a descriptive prospective study in which both bone densitometric and anthropometric data were evaluated. The inclusion criteria used were that the patients should present quadriplegic cerebral palsy, be confined to a wheelchair, be between 10 and 20 years of age and present neuromuscular scoliosis. Results We evaluated 31 patients (20 females) with a mean age of 14.2 years. Their mean biceps circumference, calf circumference and body mass index were 19.4 cm, 18.6 cm and 16.9 kg/m2, respectively. The mean standard deviation from bone densitometry was −3.2 (z-score), which characterizes osteoporosis. Conclusion There is high incidence of osteoporosis in patients with neuromuscular scoliosis secondary to quadriplegic cerebral palsy. PMID:26229882

  8. Naturally occurring plant polyphenols as potential therapies for inherited neuromuscular diseases.

    PubMed

    Fuller, Heidi R; Humphrey, Emma L; Morris, Glenn E

    2013-11-01

    There are several lines of laboratory-based evidence emerging to suggest that purified polyphenol compounds such as resveratrol, found naturally in red grapes, epigallocatechin galate from green tea and curcumin from turmeric, might be useful for the treatment of various inherited neuromuscular diseases, including spinal muscular atrophy, Duchenne muscular dystrophy and Charcot-Marie-Tooth disease. Here, we critically examine the scientific evidence related to the known molecular effects that these polyphenols have on different models of inherited neuromuscular disease, with particular attention to problems with the validity of in vitro evidence. We also present proteomic evidence that polyphenols have in vitro effects on cells related to metal ion chelation in cell-culture media. Although their precise mechanisms of action remain somewhat elusive, polyphenols could be an attractive approach to therapy for inherited neuromuscular disease, especially since they may be safer to use on young children, compared with some of the other drug candidates.

  9. Femoral quadriceps neuromuscular electrical stimulation after total knee arthroplasty: a systematic review

    PubMed Central

    Volpato, Helena Bruna Bettoni; Szego, Paulo; Lenza, Mario; Milan, Silvia Lefone; Talerman, Claudia; Ferretti, Mario

    2016-01-01

    ABSTRACT The purpose of this study was to evaluate the effects of neuromuscular electrical stimulation in patients submitted to total knee arthroplasty. This was a systematic review with no language or publication status restriction. Our search was made in Cochrane Library, MEDLINE, Embase and LILACS. Randomized or quasi-randomized clinical trials evaluating neuromuscular electrical stimulation after total knee arthroplasty were included. Four studies with moderate risk of bias and low statistical power were included, totalizing 376 participants. There was no statistically significant difference in knee function, pain and range of motion during 12 month follow-up. This review concluded that neuromuscular electrical stimulation was less effective than traditional rehabilitation in function, muscular strength and range of motion. However, this technique was useful for quadriceps activation during the first days after surgery. PMID:26537511

  10. The use of in-flight foot pressure as a countermeasure to neuromuscular degradation

    NASA Technical Reports Server (NTRS)

    Layne, C. S.; Mulavara, A. P.; Pruett, C. J.; McDonald, P. V.; Kozlovskaya, I. B.; Bloomberg, J. J.

    1998-01-01

    The purpose of this study was to determine whether applying foot pressure to unrestrained subjects during space flight could enhance the neuromuscular activation associated with rapid arm movements. Four men performed unilateral arm raises while wearing--or not wearing--specially designed boots during a 81- or 115-day space flight. Arm acceleration and surface EMG were obtained from selected lower limb and trunk muscles. Pearson r coefficients were used to evaluate similarity in phasic patterns between the two in-flight conditions. In-flight data also were magnitude normalized to the mean voltage value of the muscle activation waveforms obtained during the no-foot-pressure condition to facilitate comparison of activation amplitude between the two in-flight conditions. Foot pressure enhanced neuromuscular activation and somewhat modified the phasic features of the neuromuscular activation during the arm raises.

  11. Naturally occurring plant polyphenols as potential therapies for inherited neuromuscular diseases.

    PubMed

    Fuller, Heidi R; Humphrey, Emma L; Morris, Glenn E

    2013-11-01

    There are several lines of laboratory-based evidence emerging to suggest that purified polyphenol compounds such as resveratrol, found naturally in red grapes, epigallocatechin galate from green tea and curcumin from turmeric, might be useful for the treatment of various inherited neuromuscular diseases, including spinal muscular atrophy, Duchenne muscular dystrophy and Charcot-Marie-Tooth disease. Here, we critically examine the scientific evidence related to the known molecular effects that these polyphenols have on different models of inherited neuromuscular disease, with particular attention to problems with the validity of in vitro evidence. We also present proteomic evidence that polyphenols have in vitro effects on cells related to metal ion chelation in cell-culture media. Although their precise mechanisms of action remain somewhat elusive, polyphenols could be an attractive approach to therapy for inherited neuromuscular disease, especially since they may be safer to use on young children, compared with some of the other drug candidates. PMID:24215348

  12. Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease.

    PubMed

    Khan, Muzamil Majid; Lustrino, Danilo; Silveira, Willian A; Wild, Franziska; Straka, Tatjana; Issop, Yasmin; O'Connor, Emily; Cox, Dan; Reischl, Markus; Marquardt, Till; Labeit, Dittmar; Labeit, Siegfried; Benoit, Evelyne; Molgó, Jordi; Lochmüller, Hanns; Witzemann, Veit; Kettelhut, Isis C; Navegantes, Luiz C C; Pozzan, Tullio; Rudolf, Rüdiger

    2016-01-19

    The distribution and function of sympathetic innervation in skeletal muscle have largely remained elusive. Here we demonstrate that sympathetic neurons make close contact with neuromuscular junctions and form a network in skeletal muscle that may functionally couple different targets including blood vessels, motor neurons, and muscle fibers. Direct stimulation of sympathetic neurons led to activation of muscle postsynaptic β2-adrenoreceptor (ADRB2), cAMP production, and import of the transcriptional coactivator peroxisome proliferator-activated receptor γ-coactivator 1α (PPARGC1A) into myonuclei. Electrophysiological and morphological deficits of neuromuscular junctions upon sympathectomy and in myasthenic mice were rescued by sympathicomimetic treatment. In conclusion, this study identifies the neuromuscular junction as a target of the sympathetic nervous system and shows that sympathetic input is crucial for synapse maintenance and function. PMID:26733679

  13. Neuromuscular interaction is required for neurotrophins-mediated locomotor recovery following treadmill training in rat spinal cord injury.

    PubMed

    Wu, Qinfeng; Cao, Yana; Dong, Chuanming; Wang, Hongxing; Wang, Qinghua; Tong, Weifeng; Li, Xiangzhe; Shan, Chunlei; Wang, Tong

    2016-01-01

    Recent results have shown that exercise training promotes the recovery of injured rat distal spinal cords, but are still unclear about the function of skeletal muscle in this process. Herein, rats with incomplete thoracic (T10) spinal cord injuries (SCI) with a dual spinal lesion model were subjected to four weeks of treadmill training and then were treated with complete spinal transection at T8. We found that treadmill training allowed the retention of hind limb motor function after incomplete SCI, even with a heavy load after complete spinal transection. Moreover, treadmill training alleviated the secondary injury in distal lumbar spinal motor neurons, and enhanced BDNF/TrkB expression in the lumbar spinal cord. To discover the influence of skeletal muscle contractile activity on motor function and gene expression, we adopted botulinum toxin A (BTX-A) to block the neuromuscular activity of the rat gastrocnemius muscle. BTX-A treatment inhibited the effects of treadmill training on motor function and BDNF/TrKB expression. These results indicated that treadmill training through the skeletal muscle-motor nerve-spinal cord retrograde pathway regulated neuralplasticity in the mammalian central nervous system, which induced the expression of related neurotrophins and promoted motor function recovery. PMID:27190721

  14. Neuromuscular interaction is required for neurotrophins-mediated locomotor recovery following treadmill training in rat spinal cord injury.

    PubMed

    Wu, Qinfeng; Cao, Yana; Dong, Chuanming; Wang, Hongxing; Wang, Qinghua; Tong, Weifeng; Li, Xiangzhe; Shan, Chunlei; Wang, Tong

    2016-01-01

    Recent results have shown that exercise training promotes the recovery of injured rat distal spinal cords, but are still unclear about the function of skeletal muscle in this process. Herein, rats with incomplete thoracic (T10) spinal cord injuries (SCI) with a dual spinal lesion model were subjected to four weeks of treadmill training and then were treated with complete spinal transection at T8. We found that treadmill training allowed the retention of hind limb motor function after incomplete SCI, even with a heavy load after complete spinal transection. Moreover, treadmill training alleviated the secondary injury in distal lumbar spinal motor neurons, and enhanced BDNF/TrkB expression in the lumbar spinal cord. To discover the influence of skeletal muscle contractile activity on motor function and gene expression, we adopted botulinum toxin A (BTX-A) to block the neuromuscular activity of the rat gastrocnemius muscle. BTX-A treatment inhibited the effects of treadmill training on motor function and BDNF/TrKB expression. These results indicated that treadmill training through the skeletal muscle-motor nerve-spinal cord retrograde pathway regulated neuralplasticity in the mammalian central nervous system, which induced the expression of related neurotrophins and promoted motor function recovery.

  15. Frontoxins, three-finger toxins from Micrurus frontalis venom, decrease miniature endplate potential amplitude at frog neuromuscular junction.

    PubMed

    Moreira, K G; Prates, M V; Andrade, F A C; Silva, L P; Beirão, P S L; Kushmerick, C; Naves, L A; Bloch, C

    2010-08-01

    Neurotoxicity is a major symptom of envenomation caused by Brazilian coral snake Micrurus frontalis. Due to the small amount of material that can be collected, no neurotoxin has been fully sequenced from this venom. In this work we report six new three-finger like toxins isolated from the venom of the coral snake M. frontalis which we named Frontoxin (FTx) I-VI. Toxins were purified using multiple steps of RP-HPLC. Molecular masses were determined by MALDI-TOF and ESI ion-trap mass spectrometry. The complete amino acid sequence of FTx II, III, IV and V were determined by sequencing of overlapping proteolytic fragments by Edman degradation and by de novo sequencing. The amino acid sequences of FTx I, II, III and VI predict 4 conserved disulphide bonds and structural similarity to previously reported short-chain alpha-neurotoxins. FTx IV and V each contained 10 conserved cysteines and share high similarity with long-chain alpha-neurotoxins. At the frog neuromuscular junction FTx II, III and IV reduced miniature endplate potential amplitudes in a time-and concentration-dependent manner suggesting Frontoxins block nicotinic acetylcholine receptors.

  16. Neuromuscular interaction is required for neurotrophins-mediated locomotor recovery following treadmill training in rat spinal cord injury

    PubMed Central

    Wu, Qinfeng; Cao, Yana; Dong, Chuanming; Wang, Hongxing; Wang, Qinghua; Tong, Weifeng; Li, Xiangzhe

    2016-01-01

    Recent results have shown that exercise training promotes the recovery of injured rat distal spinal cords, but are still unclear about the function of skeletal muscle in this process. Herein, rats with incomplete thoracic (T10) spinal cord injuries (SCI) with a dual spinal lesion model were subjected to four weeks of treadmill training and then were treated with complete spinal transection at T8. We found that treadmill training allowed the retention of hind limb motor function after incomplete SCI, even with a heavy load after complete spinal transection. Moreover, treadmill training alleviated the secondary injury in distal lumbar spinal motor neurons, and enhanced BDNF/TrkB expression in the lumbar spinal cord. To discover the influence of skeletal muscle contractile activity on motor function and gene expression, we adopted botulinum toxin A (BTX-A) to block the neuromuscular activity of the rat gastrocnemius muscle. BTX-A treatment inhibited the effects of treadmill training on motor function and BDNF/TrKB expression. These results indicated that treadmill training through the skeletal muscle-motor nerve-spinal cord retrograde pathway regulated neuralplasticity in the mammalian central nervous system, which induced the expression of related neurotrophins and promoted motor function recovery. PMID:27190721

  17. Rapid feedback regulation of synaptic efficacy during high-frequency activity at the Drosophila larval neuromuscular junction

    PubMed Central

    Kauwe, Grant; Isacoff, Ehud Y.

    2013-01-01

    High-frequency firing of neurons depresses transmitter release at many synapses. At the glutamatergic synapse of the Drosophila larval neuromuscular junction, we find that presynaptic depression is modulated by postsynaptic ionotropic glutamate receptor (iGluR) activity. Although basal release at low frequency was insensitive to postsynaptic iGluR activity, recovery from depression elicited by high-frequency presynaptic trains decreased with partial block of native iGluRs. Moreover, recovery from depression increased with optical activation of the light-gated mammalian iGluR6 (LiGluR) expressed postsynaptically. The enhancement of recovery from depression occurred within 2 min of optical activation of LiGluR and persisted for minutes after optical deactivation. This effect depended on cAMP-dependent presynaptic recruitment of vesicles from the reserve pool. Our findings reveal a unique dimension to postsynaptic iGluR activity: fast retrograde signaling that preserves transmission efficacy during high-frequency presynaptic firing. PMID:23674684

  18. Effect of a 6-week dynamic neuromuscular training programme on ankle joint function: A Case report

    PubMed Central

    2011-01-01

    Background Ankle joint sprain and the subsequent development of chronic ankle instability (CAI) are commonly encountered by clinicians involved in the treatment and rehabilitation of musculoskeletal injuries. It has recently been advocated that ankle joint post-sprain rehabilitation protocols should incorporate dynamic neuromuscular training to enhance ankle joint sensorimotor capabilities. To date no studies have reported on the effects of dynamic neuromuscular training on ankle joint positioning during landing from a jump, which has been reported as one of the primary injury mechanisms for ankle joint sprain. This case report details the effects of a 6-week dynamic neuromuscular training programme on ankle joint function in an athlete with CAI. Methods The athlete took part in a progressive 6-week dynamic neuromuscular training programme which incorporated postural stability, strengthening, plyometric, and speed/agility drills. The outcome measures chosen to assess for interventional efficacy were: [1] Cumberland Ankle Instability Tool (CAIT) scores, [2] Star Excursion Balance Test (SEBT) reach distances, [3] ankle joint plantar flexion during drop landing and drop vertical jumping, and [4] ground reaction forces (GRFs) during walking. Results CAIT and SEBT scores improved following participation in the programme. The angle of ankle joint plantar flexion decreased at the point of initial contact during the drop landing and drop vertical jumping tasks, indicating that the ankle joint was in a less vulnerable position upon landing following participation in the programme. Furthermore, GRFs were reduced whilst walking post-intervention. Conclusions The 6-week dynamic neuromuscular training programme improved parameters of ankle joint sensorimotor control in an athlete with CAI. Further research is now required in a larger cohort of subjects to determine the effects of neuromuscular training on ankle joint injury risk factors. PMID:21658224

  19. Optoelectronics using block copolymers.

    SciTech Connect

    Botiz, I.; Darling, S. B.; Center for Nanoscale Materials

    2010-05-01

    Block copolymers, either as semiconductors themselves or as structure directors, are emerging as a promising class of materials for understanding and controlling processes associated with both photovoltaic energy conversion and light emitting devices.

  20. Superalloy Lattice Block Structures

    NASA Technical Reports Server (NTRS)

    Nathal, M. V.; Whittenberger, J. D.; Hebsur, M. G.; Kantzos, P. T.; Krause, D. L.

    2004-01-01

    Initial investigations of investment cast superalloy lattice block suggest that this technology will yield a low cost approach to utilize the high temperature strength and environmental resistance of superalloys in lightweight, damage tolerant structural configurations. Work to date has demonstrated that relatively large superalloy lattice block panels can be successfully investment cast from both IN-718 and Mar-M247. These castings exhibited mechanical properties consistent with the strength of the same superalloys measured from more conventional castings. The lattice block structure also accommodates significant deformation without failure, and is defect tolerant in fatigue. The potential of lattice block structures opens new opportunities for the use of superalloys in future generations of aircraft applications that demand strength and environmental resistance at elevated temperatures along with low weight.

  1. Resolving writer's block.

    PubMed Central

    Huston, P.

    1998-01-01

    PROBLEM BEING ADDRESSED: Writer's block, or a distinctly uncomfortable inability to write, can interfere with professional productivity. OBJECTIVE OF PROGRAM: To identify writer's block and to outline suggestions for its early diagnosis, treatment, and prevention. MAIN COMPONENTS OF PROGRAM: Once the diagnosis has been established, a stepwise approach to care is recommended. Mild blockage can be resolved by evaluating and revising expectations, conducting a task analysis, and giving oneself positive feedback. Moderate blockage can be addressed by creative exercises, such as brainstorming and role-playing. Recalcitrant blockage can be resolved with therapy. Writer's block can be prevented by taking opportunities to write at the beginning of projects, working with a supportive group of people, and cultivating an ongoing interest in writing. CONCLUSIONS: Writer's block is a highly treatable condition. A systematic approach can help to alleviate anxiety, build confidence, and give people the information they need to work productively. PMID:9481467

  2. Blocked tear duct

    MedlinePlus

    ... your baby may have an eye infection called conjunctivitis . ... increase the chance of other infections, such as conjunctivitis. ... be prevented. Proper treatment of nasal infections and conjunctivitis may reduce the risk of having a blocked ...

  3. Block copolymer battery separator

    DOEpatents

    Wong, David; Balsara, Nitash Pervez

    2016-04-26

    The invention herein described is the use of a block copolymer/homopolymer blend for creating nanoporous materials for transport applications. Specifically, this is demonstrated by using the block copolymer poly(styrene-block-ethylene-block-styrene) (SES) and blending it with homopolymer polystyrene (PS). After blending the polymers, a film is cast, and the film is submerged in tetrahydrofuran, which removes the PS. This creates a nanoporous polymer film, whereby the holes are lined with PS. Control of morphology of the system is achieved by manipulating the amount of PS added and the relative size of the PS added. The porous nature of these films was demonstrated by measuring the ionic conductivity in a traditional battery electrolyte, 1M LiPF.sub.6 in EC/DEC (1:1 v/v) using AC impedance spectroscopy and comparing these results to commercially available battery separators.

  4. Cell block eleven (left) and cell block fifteen, looking from ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Cell block eleven (left) and cell block fifteen, looking from cell block two into the "Death Row" exercise yard - Eastern State Penitentiary, 2125 Fairmount Avenue, Philadelphia, Philadelphia County, PA

  5. View of cell block eight (left), cell block seven, and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of cell block eight (left), cell block seven, and southwest guard tower, looking from cell block eight roof - Eastern State Penitentiary, 2125 Fairmount Avenue, Philadelphia, Philadelphia County, PA

  6. Installation of the hand influences acceleromyography measurement. A comparison with mechanomyography during neuromuscular recovery.

    PubMed

    Dubois, Ph E; Gourdin, M; Russell, K; Jamart, J

    2005-01-01

    Acceleromyography is commonly used to monitor perioperative neuromuscular blockade and to prevent residual neuromuscular blockade at the time of tracheal extubation. However, there are problems associated with this method, such as obtaining stable values, particularly beneath the surgical fields. We compared TOF ratios obtained on both hands simultaneously using on one side mechanomyography and on the other acceleromyography, installed in four different ways: the hand simply lying on a board, fingers fixed with tape, use of the hand adaptor or the TOF-tube. Further to maintaining free thumb movement, the TOF-tube improves feasibility of acceleromyography by reducing the measurement variability while retaining accuracy. PMID:16013661

  7. Superalloy Lattice Block Structures

    NASA Technical Reports Server (NTRS)

    Whittenberger, J. D.; Nathal, M. V.; Hebsur, M. G.; Kraus, D. L.

    2003-01-01

    In their simplest form, lattice block panels are produced by direct casting and result in lightweight, fully triangulated truss-like configurations which provide strength and stiffness [2]. The earliest realizations of lattice block were made from A1 and steels, primarily under funding from the US Navy [3]. This work also showed that the mechanical efficiency (eg., specific stiffness) of lattice block structures approached that of honeycomb structures [2]. The lattice architectures are also less anisotropic, and the investment casting route should provide a large advantage in cost and temperature capability over honeycombs which are limited to alloys that can be processed into foils. Based on this early work, a program was initiated to determine the feasibility of extending the high temperature superalloy lattice block [3]. The objective of this effort was to provide an alternative to intermetallics and composites in achieving a lightweight high temperature structure without sacrificing the damage tolerance and moderate cost inherent in superalloys. To establish the feasibility of the superalloy lattice block concept, work was performed in conjunction with JAMCORP, Inc. Billerica, MA, to produce a number of lattice block panels from both IN71 8 and Mar-M247.

  8. Seismicity of the Jalisco Block

    NASA Astrophysics Data System (ADS)

    Nunez-Cornu, F. J.; Rutz, M.; Camarena-Garcia, M.; Trejo-Gomez, E.; Reyes-Davila, G.; Suarez-Plascencia, C.

    2002-12-01

    In April 2002 began to transmit the stations of the first phase of Jalisco Telemetric Network located at the northwest of Jalisco Block and at the area of Volcan de Fuego (Colima Volcano), in June were deployed four additional MarsLite portable stations in the Bahia de Banderas area, and by the end of August one more portable station at Ceboruco Volcano. The data of these stations jointly with the data from RESCO (Colima Telemetric Network) give us the minimum seismic stations coverage to initiate in a systematic and permanent way the study of the seismicity in this very complex tectonic region. A preliminary analysis of seismicity based on the events registered by the networks using a shutter algorithm, confirms several important features proposed by microseismicity studies carried out between 1996 and 1998. A high level of seismicity inside and below of Rivera plate is observed, this fact suggest a very complex stress pattern acting on this plate. Shallow seismicity at south and east of Bahia de Banderas also suggest a complex stress pattern in this region of the Jalisco Block, events at more than 30 km depth are located under the mouth of the bay and in face of it, a feature denominated Banderas Boundary mark the change of the seismic regime at north of this latitude (20.75°N), however some shallow events were located at the region of Nayarit.

  9. Neuromuscular characteristics and fatigue during 10 km running.

    PubMed

    Paavolainen, L; Nummela, A; Rusko, H; Häkkinen, K

    1999-11-01

    This study investigated neuromuscular characteristics and fatigue during 10 km running (10 K) performance in well-trained endurance athletes with different distance running capability. Nine high (HC) and ten low (LC) caliber endurance athletes performed the 10 K on a 200 m indoor track, constant velocity lap (CVL, 4.5 m x s(-1)) 5 times during the course of the 10 K and maximal 20 m speed test before (20 m(b)) and after (20 m(a)) the 10 K. Running velocity (V), ground contact times (CT), ground reaction forces (F) and electromyographic activity (EMG) of the leg muscles (vastus lateralis; VL, biceps femoris; BF, gastrocnemius; GA) were measured during 20 m(b), 20 m(a), and CVLs. The 10 K times differed (p<0.001) between HC and LC (36.3+/-1.2 and 39.2+/-2.0 min, respectively) but no differences were observed in 20 m(b) velocity. The 10 K led to significant (p<0.05) decreases in V, F and integrated EMG (IEMG) and increases in CTs of 20 m(a) in both groups. No changes were observed in HC or LC in F and IEMG during the CVLs but HC showed shorter (p<0.05) mean CT of CVLs than LC. A significant correlation (r = -0.56, p<0.05) was observed between the mean CT of CVLs and velocity of 10 K (V10K). Pre-activity of GA in relation to the IEMG of the total contact phase during the CVLs was higher (p<0.05) in HC than LC. The relative IEMGs of VL and GA in the propulsion phase compared to the IEMG of the 20 m(b) were lower (p<0.05) in HC than LC. In conclusion, marked fatigue took place in both HC and LC during the 10 K but the fatigue-induced changes in maximal 20 m run did not differentiate endurance athletes with different V10K. However, a capability to produce force rapidly throughout the 10 K accompanied with optimal preactivation and contact phase activation seem to be important for 10 km running performance in well trained endurance athletes.

  10. Regeneration of the active zone at the frog neuromuscular junction

    PubMed Central

    1984-01-01

    The active zone is a unique specialization of the presynaptic membrane and is believed to be the site of transmitter release. The formation of the active zone and the relationship of this process to transmitter release were studied at reinnervated neuromuscular junctions in the frog. At different times after a nerve crush, the cutaneous pectoris muscles were examined with intracellular recording recording and freeze- fracture electron microscopy. The P face of a normal active zone typically consists of two double rows of particles lined up in a continuous segment located opposite a junctional fold. In the initial stage of reinnervation, clusters of large intramembrane particles surrounding membrane elevations appeared on the P face of nerve terminals. Like normal active zones, these clusters were aligned with junctional folds. Vesicle openings, which indicate transmitter release, were seen at these primitive active zones, even though intramembrane particles were not yet organized into the normal pattern of two double rows. The length of active zones at this stage was only approximately 15% of normal. During the secondary stage, every junction was reinnervated and most active zones had begun to organize into the normal pattern with normal orientation. Unlike normal, there were often two or more discontinuous short segments of active zone aligned with the same junctional fold. The total length of active zone per junctional fold increased to one-third of normal, mainly because of the greater number of segments. In the third stage, the number of active zone segments per junctional fold showed almost no change when compared with the secondary stage. However, individual segments elongated and increased the total length of all active zone segments per junctional fold to about two-thirds of the normal length. The dynamic process culminated in the final stage, during which elongating active zones appeared to join together and the number of active zone segments per

  11. Growing Up with Their Blocks.

    ERIC Educational Resources Information Center

    Winarski, Diana L.

    1995-01-01

    Describes one teacher's use of traditional wooden blocks in fifth-grade curriculum. Notes that use of blocks can teach communication, teamwork, precision, and arithmetic concepts. Also describes four easy classroom block projects. (TM)

  12. Juvenile Accountability Block Grants Program Reauthorization Act of 2013

    THOMAS, 113th Congress

    Rep. Scott, Robert C. "Bobby" [D-VA-3

    2013-06-13

    07/15/2013 Referred to the Subcommittee on Crime, Terrorism, Homeland Security, and Investigations. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  13. Blockade of ActRIIB Signaling Triggers Muscle Fatigability and Metabolic Myopathy

    PubMed Central

    Relizani, Karima; Mouisel, Etienne; Giannesini, Benoit; Hourdé, Christophe; Patel, Ketan; Morales Gonzalez, Susanne; Jülich, Kristina; Vignaud, Alban; Piétri-Rouxel, France; Fortin, Dominique; Garcia, Luis; Blot, Stéphane; Ritvos, Olli; Bendahan, David; Ferry, Arnaud; Ventura-Clapier, Renée; Schuelke, Markus; Amthor, Helge

    2014-01-01

    Myostatin regulates skeletal muscle size via the activin receptor IIB (ActRIIB). However, its effect on muscle energy metabolism and energy-dependent muscle function remains largely unexplored. This question needs to be solved urgently since various therapies for neuromuscular diseases based on blockade of ActRIIB signaling are being developed. Here, we show in mice, that 4-month pharmacological abrogation of ActRIIB signaling by treatment with soluble ActRIIB-Fc triggers extreme muscle fatigability. This is associated with elevated serum lactate levels and a severe metabolic myopathy in the mdx mouse, an animal model of Duchenne muscular dystrophy. Blockade of ActRIIB signaling downregulates porin, a crucial ADP/ATP shuttle between cytosol and mitochondrial matrix leading to a consecutive deficiency of oxidative phosphorylation as measured by in vivo Phophorus Magnetic Resonance Spectroscopy (31P-MRS). Further, ActRIIB blockade reduces muscle capillarization, which further compounds the metabolic stress. We show that ActRIIB regulates key determinants of muscle metabolism, such as Pparβ, Pgc1α, and Pdk4 thereby optimizing different components of muscle energy metabolism. In conclusion, ActRIIB signaling endows skeletal muscle with high oxidative capacity and low fatigability. The severe metabolic side effects following ActRIIB blockade caution against deploying this strategy, at least in isolation, for treatment of neuromuscular disorders. PMID:24861054

  14. Effect of magnesium sulphate on sugammadex reversal time for neuromuscular blockade: a randomised controlled study.

    PubMed

    Germano Filho, P A; Cavalcanti, I L; Barrucand, L; Verçosa, N

    2015-08-01

    Magnesium potentiates neuromuscular blockade. Sugammadex reverses rocuronium-induced blockade. The aim of this study was to determine the effect of pre-treatment with magnesium sulphate on sugammadex reversal time for neuromuscular blockade. Seventy-three patients were randomly assigned to receive magnesium sulphate (40 mg.kg(-1) ) or saline intravenously. After anaesthetic induction, continuous train-of-four monitoring was performed and rocuronium was administered (0.6 mg.kg(-1) ). When a second twitch appeared, the patients received sugammadex (2 mg.kg(-1) ). The median (IQR [range]) reversal time of moderate neuromuscular blockade to a train-of-four ratio of 0.9 facilitated by sugammadex was 115 (93-177.5 [68-315]) s in the magnesium group and 120 (105-140 [70-298]) s in the saline group (p = 0.79). The median (IQR [range]) clinical duration was 45 (35.5-53 [22-102]) min in the magnesium group and 37 (31-43 [19-73]) min in the saline group (p = 0.031). Pre-treatment with magnesium did not significantly affect sugammadex reversal time of moderate neuromuscular blockade induced by rocuronium.

  15. A Distinct Perisynaptic Glial Cell Type Forms Tripartite Neuromuscular Synapses in the Drosophila Adult

    PubMed Central

    Strauss, Alexandra L.; Kawasaki, Fumiko; Ordway, Richard W.

    2015-01-01

    Previous studies of Drosophila flight muscle neuromuscular synapses have revealed their tripartite architecture and established an attractive experimental model for genetic analysis of glial function in synaptic transmission. Here we extend these findings by defining a new Drosophila glial cell type, designated peripheral perisynaptic glia (PPG), which resides in the periphery and interacts specifically with fine motor axon branches forming neuromuscular synapses. Identification and specific labeling of PPG was achieved through cell type-specific RNAi-mediated knockdown (KD) of a glial marker, Glutamine Synthetase 2 (GS2). In addition, comparison among different Drosophila neuromuscular synapse models from adult and larval developmental stages indicated the presence of tripartite synapses on several different muscle types in the adult. In contrast, PPG appear to be absent from larval body wall neuromuscular synapses, which do not exhibit a tripartite architecture but rather are imbedded in the muscle plasma membrane. Evolutionary conservation of tripartite synapse architecture and peripheral perisynaptic glia in vertebrates and Drosophila suggests ancient and conserved roles for glia-synapse interactions in synaptic transmission. PMID:26053860

  16. Exercise-induced dehydration does not alter time trial or neuromuscular performance.

    PubMed

    Stewart, C J; Whyte, D G; Cannon, J; Wickham, J; Marino, F E

    2014-08-01

    This study examined the effect of exercise-induced dehydration by ~4% body mass loss on 5-km cycling time trial (TT) performance and neuromuscular drive, independent of hyperthermia. 7 active males were dehydrated on 2 occasions, separated by 7 d. Participants remained dehydrated (DEH, -3.8±0.5%) or were rehydrated (REH, 0.2±0.6%) over 2 h before completing the TT at 18-25 °C, 20-30% relative humidity. Neuromuscular function was determined before dehydration and immediately prior the TT. The TT started at the same core temperature (DEH, 37.3±0.3°C; REH, 37.0±0.2 °C (P>0.05). Neither TT performance (DEH, 7.31±1.5 min; REH, 7.10±1.3 min (P>0.05)) or % voluntary activation were affected by dehydration (DEH, 88.7±6.4%; REH, 90.6±6.1% (P>0.05)). Quadriceps peak torque was significantly elevated in both trials prior to the TT (P<0.05), while a 19% increase in the rate of potentiated peak twitch torque development (P<0.05) was observed in the DEH trial only. All other neuromuscular measures were similar between trials. Short duration TT performance and neuromuscular function are not reduced by dehydration, independent of hyperthermia.

  17. Current Methodological Issues in the Study of Children with Inherited Neuromuscular Disorders

    ERIC Educational Resources Information Center

    Mercuri, Eugenio; Messina, Sonia; Pane, Marika; Bertini, Enrico

    2008-01-01

    Several clinical trials assessing children with hereditary neuromuscular disorders have been performed over the last decade. These studies highlighted issues related to design and performance of clinical studies assessing children with this group of disorders. This article reviews recent literature and clinical experience in this area,…

  18. Evidence-Based Systematic Review: Effects of Neuromuscular Electrical Stimulation on Swallowing and Neural Activation

    ERIC Educational Resources Information Center

    Clark, Heather; Lazarus, Cathy; Arvedson, Joan; Schooling, Tracy; Frymark, Tobi

    2009-01-01

    Purpose: To systematically review the literature examining the effects of neuromuscular electrical stimulation (NMES) on swallowing and neural activation. The review was conducted as part of a series examining the effects of oral motor exercises (OMEs) on speech, swallowing, and neural activation. Method: A systematic search was conducted to…

  19. Short day lengths delay development of the SNB neuromuscular system in the Siberian hamster, Phodopus sungorus.

    PubMed

    Hegstrom, C D; Breedlove, S M

    1998-06-15

    The Siberian hamster, Phodopus sungorus, breeds seasonally. In the laboratory, the seasonal breeding can be controlled by photoperiod, which affects the durations of nightly melatonin secretions. Winterlike short day lengths induce gonadal regression in adult animals, and pups born and maintained in short days undergo gonadal development much later than animals born into long days. The spinal nucleus of the bulbocavernosus (SNB) and its target muscles, the bulbocavernosus (BC) and levator ani (LA), comprise a sexually dimorphic, androgensensitive neuromuscular system involved in male reproduction. The SNB neuromuscular system was studied in male Siberian hamsters maintained from conception in short-day (8:16 h light/dark cycle) versus long-day (16:8 h light/dark cycle) conditions. At 40-47 days of age, development of three components of the SNB neuromuscular system were all significantly delayed in hamsters raised in the short photoperiod: BC/LA muscle weight, the size of SNB motoneuronal somata, and the area of the neuromuscular junctions at the BC/LA muscles of short-day hamsters were each significantly reduced relative to those of longday counterparts. Thus, development of the SNB reproductive system is delayed under short day lengths in this species.

  20. Proprioceptive Neuromuscular Facilitation Flexibility Techniques: Acute Effects on Arterial Blood Pressure.

    ERIC Educational Resources Information Center

    Cornelius, William L.; Craft-Hamm, Kelley

    1988-01-01

    The effects of stretching techniques on arterial blood pressure (ABP) were studied in three groups of 20 men each. Each group performed one of three proprioceptive neuromuscular facilitation (PNF) techniques. Results are presented. The study indicates that the benefits of stretching may outweigh the risk of elevated ABP. (JL)

  1. A system for studying mechanisms of neuromuscular junction development and maintenance

    PubMed Central

    Vilmont, Valérie; Ouanounou, Gilles

    2016-01-01

    The neuromuscular junction (NMJ), a cellular synapse between a motor neuron and a skeletal muscle fiber, enables the translation of chemical cues into physical activity. The development of this special structure has been subject to numerous investigations, but its complexity renders in vivo studies particularly difficult to perform. In vitro modeling of the neuromuscular junction represents a powerful tool to delineate fully the fine tuning of events that lead to subcellular specialization at the pre-synaptic and post-synaptic sites. Here, we describe a novel heterologous co-culture in vitro method using rat spinal cord explants with dorsal root ganglia and murine primary myoblasts to study neuromuscular junctions. This system allows the formation and long-term survival of highly differentiated myofibers, motor neurons, supporting glial cells and functional neuromuscular junctions with post-synaptic specialization. Therefore, fundamental aspects of NMJ formation and maintenance can be studied using the described system, which can be adapted to model multiple NMJ-associated disorders. PMID:27226316

  2. A system for studying mechanisms of neuromuscular junction development and maintenance.

    PubMed

    Vilmont, Valérie; Cadot, Bruno; Ouanounou, Gilles; Gomes, Edgar R

    2016-07-01

    The neuromuscular junction (NMJ), a cellular synapse between a motor neuron and a skeletal muscle fiber, enables the translation of chemical cues into physical activity. The development of this special structure has been subject to numerous investigations, but its complexity renders in vivo studies particularly difficult to perform. In vitro modeling of the neuromuscular junction represents a powerful tool to delineate fully the fine tuning of events that lead to subcellular specialization at the pre-synaptic and post-synaptic sites. Here, we describe a novel heterologous co-culture in vitro method using rat spinal cord explants with dorsal root ganglia and murine primary myoblasts to study neuromuscular junctions. This system allows the formation and long-term survival of highly differentiated myofibers, motor neurons, supporting glial cells and functional neuromuscular junctions with post-synaptic specialization. Therefore, fundamental aspects of NMJ formation and maintenance can be studied using the described system, which can be adapted to model multiple NMJ-associated disorders. PMID:27226316

  3. Family Stress with Chronic Childhood Illness: Cystic Fibrosis, Neuromuscular Disease, and Renal Disease.

    ERIC Educational Resources Information Center

    Holroyd, Jean; Guthrie, Donald

    1986-01-01

    Parents of children with neuromuscular disease, cystic fibrosis, and renal disease were compared with parents of control subjects matched by age to the clinical cases. The three clinical groups exhibited different patterns of stressful response, consistent with the nature of their illnesses and the requirements for care imposed on the families.…

  4. Metabolic, cardiorespiratory, and neuromuscular fitness performance in children with cerebral palsy: A comparison with healthy youth.

    PubMed

    García, Claudia Cardona; Alcocer-Gamboa, Alberto; Ruiz, Margarita Pérez; Caballero, Ignacio Martínez; Faigenbaum, Avery D; Esteve-Lanao, Jonathan; Saiz, Beatriz Moral; Lorenzo, Teresa Martín; Lara, Sergio Lerma

    2016-04-01

    The aim of this study was to assess metabolic, cardiorespiratory, and neuromuscular fitness parameters in children with spastic cerebral palsy (CP) and to compare these findings with typically developing children. 40 children with CP (21 males, 19 females; mean age, 11.0±3.3 yr; range, 6.5-17.1 yr; Gross Motor Function Classification System levels 1 or 2) and 40 healthy, age- and sex-matched children completed a test battery that consisted of 8 tests and 28 measures that assessed cardio-respiratory fitness, energy expenditure, anaerobic endurance, muscle strength, agility, stability and flexibility. Children with CP had significantly lower performance (P<0.05) on most cardiorespiratory and metabolic tests than those of healthy children, Differences in neuromuscular measures of muscular strength, speed, agility, anaerobic endurance, and flexibility between groups were most apparent. Grouped differences in cardiorespiratory variables revealed a 25% difference in performance, whereas grouped differences in metabolic and neuromuscular measures were 43% and 60%, respectively. The physical fitness of contemporary children with CP is significantly less than healthy, age-matched children. Significant differences in neuromuscular measures between groups can aid in the identification of specific fitness abilities in need of improvement in this population. PMID:27162775

  5. Decreased muscle endurance associated with diabetic neuropathy may be attributed partially to neuromuscular transmission failure.

    PubMed

    Allen, Matti D; Kimpinski, Kurt; Doherty, Timothy J; Rice, Charles L

    2015-04-15

    Diabetic polyneuropathy (DPN) can cause muscle atrophy, weakness, contractile slowing, and neuromuscular transmission instability. Our objective was to assess the response of the impaired neuromuscular system of DPN in humans when stressed with a sustained maximal voluntary contraction (MVC). Baseline MVC and evoked dorsiflexor contractile properties were assessed in DPN patients (n = 10) and controls (n = 10). Surface electromyography was used to record tibialis anterior evoked maximal compound muscle action potentials (CMAPs) and neuromuscular activity during MVCs. Participants performed a sustained isometric dorsiflexion MVC for which task termination was determined by the inability to sustain ≥60% MVC torque. The fatigue protocol was immediately followed by a maximal twitch, with additional maximal twitches and MVCs assessed at 30 s and 2 min postfatigue. DPN patients fatigued ∼21% more quickly than controls (P < 0.05) and featured less relative electromyographic activity during the first one-third of the fatigue protocol compared with controls (P < 0.05). Immediately following fatigue, maximal twitch torque was reduced similarly (∼20%) in both groups, and concurrently CMAPs were reduced (∼12%) in DPN patients, whereas they were unaffected in controls (P > 0.05). Twitch torque and CMAP amplitude recovered to baseline 30 s postfatigue. Additionally, at 30 s postfatigue, both groups had similar (∼10%) reductions in MVC torque relative to baseline, and MVC strength recovered by 2 min postfatigue. We conclude DPN patients possess less endurance than controls, and neuromuscular transmission failure may contribute to this greater fatigability. PMID:25663671

  6. Metabolic, cardiorespiratory, and neuromuscular fitness performance in children with cerebral palsy: A comparison with healthy youth

    PubMed Central

    García, Claudia Cardona; Alcocer-Gamboa, Alberto; Ruiz, Margarita Pérez; Caballero, Ignacio Martínez; Faigenbaum, Avery D.; Esteve-Lanao, Jonathan; Saiz, Beatriz Moral; Lorenzo, Teresa Martín; Lara, Sergio Lerma

    2016-01-01

    The aim of this study was to assess metabolic, cardiorespiratory, and neuromuscular fitness parameters in children with spastic cerebral palsy (CP) and to compare these findings with typically developing children. 40 children with CP (21 males, 19 females; mean age, 11.0±3.3 yr; range, 6.5–17.1 yr; Gross Motor Function Classification System levels 1 or 2) and 40 healthy, age- and sex-matched children completed a test battery that consisted of 8 tests and 28 measures that assessed cardio-respiratory fitness, energy expenditure, anaerobic endurance, muscle strength, agility, stability and flexibility. Children with CP had significantly lower performance (P<0.05) on most cardiorespiratory and metabolic tests than those of healthy children, Differences in neuromuscular measures of muscular strength, speed, agility, anaerobic endurance, and flexibility between groups were most apparent. Grouped differences in cardiorespiratory variables revealed a 25% difference in performance, whereas grouped differences in metabolic and neuromuscular measures were 43% and 60%, respectively. The physical fitness of contemporary children with CP is significantly less than healthy, age-matched children. Significant differences in neuromuscular measures between groups can aid in the identification of specific fitness abilities in need of improvement in this population. PMID:27162775

  7. Decreased muscle endurance associated with diabetic neuropathy may be attributed partially to neuromuscular transmission failure

    PubMed Central

    Kimpinski, Kurt; Doherty, Timothy J.; Rice, Charles L.

    2015-01-01

    Diabetic polyneuropathy (DPN) can cause muscle atrophy, weakness, contractile slowing, and neuromuscular transmission instability. Our objective was to assess the response of the impaired neuromuscular system of DPN in humans when stressed with a sustained maximal voluntary contraction (MVC). Baseline MVC and evoked dorsiflexor contractile properties were assessed in DPN patients (n = 10) and controls (n = 10). Surface electromyography was used to record tibialis anterior evoked maximal compound muscle action potentials (CMAPs) and neuromuscular activity during MVCs. Participants performed a sustained isometric dorsiflexion MVC for which task termination was determined by the inability to sustain ≥60% MVC torque. The fatigue protocol was immediately followed by a maximal twitch, with additional maximal twitches and MVCs assessed at 30 s and 2 min postfatigue. DPN patients fatigued ∼21% more quickly than controls (P < 0.05) and featured less relative electromyographic activity during the first one-third of the fatigue protocol compared with controls (P < 0.05). Immediately following fatigue, maximal twitch torque was reduced similarly (∼20%) in both groups, and concurrently CMAPs were reduced (∼12%) in DPN patients, whereas they were unaffected in controls (P > 0.05). Twitch torque and CMAP amplitude recovered to baseline 30 s postfatigue. Additionally, at 30 s postfatigue, both groups had similar (∼10%) reductions in MVC torque relative to baseline, and MVC strength recovered by 2 min postfatigue. We conclude DPN patients possess less endurance than controls, and neuromuscular transmission failure may contribute to this greater fatigability. PMID:25663671

  8. Man-Machine Interface System for Neuromuscular Training and Evaluation Based on EMG and MMG Signals

    PubMed Central

    de la Rosa, Ramon; Alonso, Alonso; Carrera, Albano; Durán, Ramon; Fernández, Patricia

    2010-01-01

    This paper presents the UVa-NTS (University of Valladolid Neuromuscular Training System), a multifunction and portable Neuromuscular Training System. The UVa-NTS is designed to analyze the voluntary control of severe neuromotor handicapped patients, their interactive response, and their adaptation to neuromuscular interface systems, such as neural prostheses or domotic applications. Thus, it is an excellent tool to evaluate the residual muscle capabilities in the handicapped. The UVa-NTS is composed of a custom signal conditioning front-end and a computer. The front-end electronics is described thoroughly as well as the overall features of the custom software implementation. The software system is composed of a set of graphical training tools and a processing core. The UVa-NTS works with two classes of neuromuscular signals: the classic myoelectric signals (MES) and, as a novelty, the myomechanic signals (MMS). In order to evaluate the performance of the processing core, a complete analysis has been done to classify its efficiency and to check that it fulfils with the real-time constraints. Tests were performed both with healthy and selected impaired subjects. The adaptation was achieved rapidly, applying a predefined protocol for the UVa-NTS set of training tools. Fine voluntary control was demonstrated to be reached with the myoelectric signals. And the UVa-NTS demonstrated to provide a satisfactory voluntary control when applying the myomechanic signals. PMID:22163515

  9. Man-machine interface system for neuromuscular training and evaluation based on EMG and MMG signals.

    PubMed

    de la Rosa, Ramon; Alonso, Alonso; Carrera, Albano; Durán, Ramon; Fernández, Patricia

    2010-01-01

    This paper presents the UVa-NTS (University of Valladolid Neuromuscular Training System), a multifunction and portable Neuromuscular Training System. The UVa-NTS is designed to analyze the voluntary control of severe neuromotor handicapped patients, their interactive response, and their adaptation to neuromuscular interface systems, such as neural prostheses or domotic applications. Thus, it is an excellent tool to evaluate the residual muscle capabilities in the handicapped. The UVa-NTS is composed of a custom signal conditioning front-end and a computer. The front-end electronics is described thoroughly as well as the overall features of the custom software implementation. The software system is composed of a set of graphical training tools and a processing core. The UVa-NTS works with two classes of neuromuscular signals: the classic myoelectric signals (MES) and, as a novelty, the myomechanic signals (MMS). In order to evaluate the performance of the processing core, a complete analysis has been done to classify its efficiency and to check that it fulfils with the real-time constraints. Tests were performed both with healthy and selected impaired subjects. The adaptation was achieved rapidly, applying a predefined protocol for the UVa-NTS set of training tools. Fine voluntary control was demonstrated to be reached with the myoelectric signals. And the UVa-NTS demonstrated to provide a satisfactory voluntary control when applying the myomechanic signals.

  10. A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia

    PubMed Central

    Pannérec, Alice; Ireland, Alex; Piasecki, Mathew; Karaz, Sonia; Jacot, Guillaume; Métairon, Sylviane; Danenberg, Esther; Raymond, Frédéric; Descombes, Patrick; McPhee, Jamie S.; Feige, Jerome N.

    2016-01-01

    Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process. PMID:27019136

  11. Neurophysiological Strategies for the Diagnosis of Disorders of the Neuromuscular Junction in Children

    ERIC Educational Resources Information Center

    Pitt, Matthew

    2008-01-01

    The disorders of the neuromuscular junction seen in children, the congenital myasthenic syndromes and autoimmune myasthenia gravis, are very rare. Their clinical symptoms and signs may be variable, most notably in the neonate and infant. They should enter the differential diagnosis of many different clinical presentations, such as "floppy infant"…

  12. Differential expression of active zone proteins in neuromuscular junctions suggests functional diversification.

    PubMed

    Juranek, Judyta; Mukherjee, Konark; Rickmann, Michael; Martens, Henrik; Calka, Jaroslaw; Südhof, Thomas C; Jahn, Reinhard

    2006-12-01

    Nerve terminals of the central nervous system (CNS) contain specialized release sites for synaptic vesicles, referred to as active zones. They are characterized by electron-dense structures that are tightly associated with the presynaptic plasma membrane and organize vesicle docking and priming sites. Recently, major protein constituents of active zones have been identified, including the proteins Piccolo, Bassoon, RIM, Munc13, ERCs/ELKs/CASTs and liprins. While it is becoming apparent that each of these proteins is essential for synaptic function in the CNS, it is not known to what extent these proteins are involved in synaptic function of the peripheral nervous system. Somatic neuromuscular junctions contain morphologically and functionally defined active zones with similarities to CNS synapses. In contrast, sympathetic neuromuscular varicosities lack active zone-like morphological specializations. Using immunocytochemistry at the light and electron microscopic level we have now performed a systematic investigation of all five major classes of active zone proteins in peripheral neuromuscular junctions. Our results show that somatic neuromuscular endplates contain a full complement of all active zone proteins. In contrast, varicosities of the vas deferens contain a subset of active zone proteins including Bassoon and ELKS2, with the other four components being absent. We conclude that Bassoon and ELKS2 perform independent and specialized functions in synaptic transmission of autonomic synapses.

  13. Muscle ultrasound in children: normal values and application to neuromuscular disorders.

    PubMed

    Maurits, Natalia Maria; Beenakker, Ernesto Alexander Christiaan; van Schaik, David Eric Christiaan; Fock, Johanna Maria; van der Hoeven, Johannes Harmen

    2004-08-01

    In this study, 105 healthy children (45 to 156 months old, 57 girls) were examined using ultrasound (US) imaging to obtain reference values of muscle dimensional and aspect parameters. We measured biceps and quadriceps sizes and subcutaneous tissue thickness. To quantify muscle aspect, we calculated muscle density, inhomogeneity and white-area index by digital image analysis. Age-, weight- and gender-dependencies were discussed. We demonstrated earlier that the complete set of parameters allows for differentiation between myopathies and neuropathies in adults, with high sensitivity. In this study, we investigated if these parameters have additional value in the diagnostic evaluation of 36 children with proven neuromuscular disease (20 Duchenne muscular dystrophy, 16 neuropathies). We found that density analysis provides a sensitive method for distinguishing between healthy children and children with neuromuscular disorders. We have also found that more detailed aspect analysis is necessary to further distinguish between these types of neuromuscular disorders in children. In conclusion, this set of normal muscle parameters can be used to help diagnose neuromuscular disorders in children. It will also facilitate follow-up in disease progression and therapy.

  14. Neuromuscular Adaptations to Eccentric Strength Training in Children and Adolescents with Cerebral Palsy

    ERIC Educational Resources Information Center

    Reid, Siobhan; Hamer, Peter; Alderson, Jacqueline; Lloyd, David

    2010-01-01

    Aim: To determine the neuromuscular outcomes of an eccentric strength-training programme for children and adolescents with cerebral palsy (CP). Method: In this randomised, parallel-group trial with waiting control, 14 participants with CP (six males, eight females; mean age 11y, SD 2y range 9-15y), diagnosed with upper-limb spasticity were…

  15. Adaptation of neuromuscular activation patterns during treadmill walking after long-duration space flight

    NASA Astrophysics Data System (ADS)

    Layne, C. S.; Lange, G. W.; Pruett, C. J.; McDonald, P. V.; Merkle, L. A.; Mulavara, A. P.; Smith, S. L.; Kozlovskaya, I. B.; Bloomberg, J. J.

    The precise neuromuscular control needed for optimal locomotion, particularly around heel strike and toe off, is known to be compromised after short duration (8- to 15-day) space flight. We hypothesized here that longer exposure to weightlessness would result in maladaptive neuromuscular activation during postflight treadmill walking. We also hypothesized that space flight would affect the ability of the sensory-motor control system to generate adaptive neuromuscular activation patterns in response to changes in visual target distance during postflight treadmill walking. Seven crewmembers, who completed 3- to 6-month missions, walked on a motorized treadmill while visually fixating on a target placed 30 cm (NEAR) or 2 m (FAR) from the subject's eyes. Electronic foot switch data and surface electromyography were collected from selected muscles of the right lower limb. Results indicate that the phasic features of neuromuscular activation were moderately affected and the relative amplitude of activity in the tibialis anterior and rectus femoris around toe off changed after space flight. Changes also were evident after space flight in how these muscles adapted to the shift in visual target distance.

  16. Pharyngeal neuromuscular dysfunction associated with bilateral guttural pouch tympany in a foal

    PubMed Central

    Bell, Chris

    2007-01-01

    A 2-month-old warmblood filly was presented for a 1-week history of a large, nonpainful, fluctuant swelling of the parotid and laryngeal area. Bilateral guttural pouch tympany was diagnosed. Surgical correction resolved the guttural pouch tympany; however, postoperative pharyngeal neuromuscular dysfunction developed. PMID:17334035

  17. Pharyngeal neuromuscular dysfunction associated with bilateral guttural pouch tympany in a foal.

    PubMed

    Bell, Chris

    2007-02-01

    A 2-month-old warmblood filly was presented for a 1-week history of a large, nonpainful, fluctuant swelling of the parotid and laryngeal area. Bilateral guttural pouch tympany was diagnosed. Surgical correction resolved the guttural pouch tympany; however, postoperative pharyngeal neuromuscular dysfunction developed. PMID:17334035

  18. Mirror Visual Feedback Induces Lower Neuromuscular Activity in Children with Spastic Hemiparetic Cerebral Palsy

    ERIC Educational Resources Information Center

    Feltham, Max G.; Ledebt, Annick; Deconinck, Frederik J. A.; Savelsbergh, Geert J. P.

    2010-01-01

    The study examined the effects of mirror feedback information on neuromuscular activation during bimanual coordination in eight children with spastic hemiparetic cerebral palsy (SHCP) and a matched control group. The "mirror box" creates a visual illusion, which gives rise to a visual perception of a zero lag, symmetric movement between the two…

  19. Reversal of profound neuromuscular blockade with sugammadex in an infant after bronchial foreign body removal.

    PubMed

    Azizoglu, Mustafa; Birbicer, Handan; Memis, Suleyman; Taşkınlar, Hakan

    2016-09-01

    Sugammadex is a selective chemical agent that can reverse neuromuscular blockade induced by vecuronium and rocuronium. The aim of this report is to discuss the effectiveness of sugammadex in the reversal of neuromuscular blockade in children younger than 2 years. A 16-month-old boy, weighing 10 kg, was admitted to the pediatric emergency department due to choking, cyanosis, and severe respiratory distress that occurred while he was eating peanuts. In the emergency department, the patient's condition deteriorated, and he went into respiratory arrest. He was immediately intubated and taken to the operating room. A rigid bronchoscopy was performed under general anesthesia, with administration of intravenous pentothal (5 mg/kg), rocuronium (0.6 mg/kg), and fentanyl (0.5 μg/kg) in the operating room. The foreign body was removed within 6 minutes, and the profound neuromuscular blockade was reversed with a dose of 2 mg/kg sugammadex. He was extubated successfully after obtaining the spontaneous respiratory activity, and adequate breathing was restored. Clinical use of sugammadex in children younger than 2 years is not recommended because of the lack of clinical studies. In this case report, the profound neuromuscular blockade was successfully reversed with a dose of 2 mg/kg sugammadex in a 16-month-old boy. However, more prospective clinical studies are required for the safe use of this agent in children. PMID:27555184

  20. Enhancement of neuromuscular dynamics and strength behavior using extremely low magnitude mechanical signals in mice.

    PubMed

    Mettlach, Gabriel; Polo-Parada, Luis; Peca, Lauren; Rubin, Clinton T; Plattner, Florian; Bibb, James A

    2014-01-01

    Exercise in general, and mechanical signals in particular, help ameliorate the neuromuscular symptoms of aging and possibly other neurodegenerative disorders by enhancing muscle function. To better understand the salutary mechanisms of such physical stimuli, we evaluated the potential for low intensity mechanical signals to promote enhanced muscle dynamics. The effects of daily brief periods of low intensity vibration (LIV) on neuromuscular functions and behavioral correlates were assessed in mice. Physiological analysis revealed that LIV increased isometric force production in semitendinosus skeletal muscle. This effect was evident in both young and old mice. Isometric force recordings also showed that LIV reduced the fatiguing effects of intensive synaptic muscle stimulation. Furthermore, LIV increased evoked neurotransmitter release at neuromuscular synapses but had no effect on spontaneous end plate potential amplitude or frequency. In behavioral studies, LIV increased mouse grip strength and potentiated initial motor activity in a novel environment. These results provide evidence for the efficacy of LIV in producing changes in the neuromuscular system that translate into performance gains at a behavioral scale.

  1. The concept behind sugammadex.

    PubMed

    Epemolu, O; Bom, A

    2014-05-01

    Sugammadex is the first selective relaxant binding agent. It allows rapid reversal of any degree of neuromuscular blockade induced by steroidal neuromuscular blocking agents. Sugammadex acts by encapsulation of the neuromuscular blocking agent. This prevents the drug from acting on prejunctional and postjunctional nicotinic receptors, allowing acetylcholine to activate these receptors, and resulting in reversal of the neuromuscular blockade. Objective monitoring of the degree of neuromuscular blockade is strongly recommended to determine the optimal dose of sugammadex. A good understanding of the concept behind sugammadex is essential in order to use this reversal agent in clinical practice.

  2. Neuromuscular adverse effects associated with systemic retinoid dermatotherapy: monitoring and treatment algorithm for clinicians.

    PubMed

    Chroni, Elisabeth; Monastirli, Alexandra; Tsambaos, Dionysios

    2010-01-01

    Although neuromuscular adverse effects represent significant clinical manifestations of hypervitaminosis A syndrome, surprisingly little attention has been paid to the potential neuromuscular toxicity of vitamin A derivatives (retinoids). Since isotretinoin and acitretin are currently the two most commonly used oral retinoids in systemic dermatotherapy, this review focuses exclusively on their neuromuscular adverse effects and proposes a neuromuscular algorithm for appropriate monitoring of patients treated with these two compounds. The most frequent CNS adverse effect associated with oral isotretinoin is headache, either as an independent adverse effect or as part of benign intracranial hypertension, which is additionally characterized by nausea and visual changes. Isolated cases of stiff-person-like syndrome, epileptic seizures and generalized muscle stiffness syndrome, possibly or probably related to oral treatment with isotretinoin, have also been reported. In addition, oral isotretinoin has reportedly been associated with muscular adverse effects that most frequently manifest as myalgia and stiffness and, in rare cases, as true myopathy or rhabdomyolysis. Creatine phosphokinase, a specific marker of muscle destruction, has been found to be elevated, occasionally by up to 100 times the normal value (with or without muscular symptoms and signs), in a variable percentage of patients receiving isotretinoin treatment and particularly in those undergoing vigorous physical exercise. Oral acitretin has been found to cause peripheral nerve dysfunction, particularly of sensory fibres, which in rare cases leads to clinically evident sensory disturbances. Less clear is the causal relationship between acitretin and benign intracranial hypertension or myopathy, whereas an isolated case of cranial nerve IV (oculomotor) palsy and a further case of thrombotic stroke during treatment with oral acitretin have been reported. Systemic diseases with involvement of nervous and

  3. Genetic modifiers of ambulation in the cooperative international Neuromuscular research group Duchenne natural history study

    PubMed Central

    Bello, Luca; Kesari, Akanchha; Gordish-Dressman, Heather; Cnaan, Avital; Morgenroth, Lauren P; Punetha, Jaya; Duong, Tina; Henricson, Erik K; Pegoraro, Elena; McDonald, Craig M; Hoffman, Eric P

    2015-01-01

    Objective We studied the effects of LTBP4 and SPP1 polymorphisms on age at loss of ambulation (LoA) in a multiethnic Duchenne muscular dystrophy (DMD) cohort. Methods We genotyped SPP1 rs28357094 and LTBP4 haplotype in 283 of 340 participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG-DNHS). Median ages at LoA were compared by Kaplan–Meier analysis and log-rank test. We controlled polymorphism analyses for concurrent effects of glucocorticoid corticosteroid (GC) treatment (time-varying Cox regression) and for population stratification (multidimensional scaling of genome-wide markers). Results Hispanic and South Asian participants (n = 18, 41) lost ambulation 2.7 and 2 years earlier than Caucasian subjects (p = 0.003, <0.001). The TG/GG genotype at SPP1 rs28357094 was associated to 1.2-year-earlier median LoA (p = 0.048). This difference was greater (1.9 years, p = 0.038) in GC-treated participants, whereas no difference was observed in untreated subjects. Cox regression confirmed a significant effect of SPP1 genotype in GC-treated participants (hazard ratio = 1.61, p = 0.016). LTBP4 genotype showed a direction of association with age at LoA as previously reported, but it was not statistically significant. After controlling for population stratification, we confirmed a strong effect of LTBP4 genotype in Caucasians (2.4 years, p = 0.024). Median age at LoA with the protective LTBP4 genotype in this cohort was 15.0 years, 16.0 for those who were treated with GC. Interpretation SPP1 rs28357094 acts as a pharmacodynamic biomarker of GC response, and LTBP4 haplotype modifies age at LoA in the CINRG-DNHS cohort. Adjustment for GC treatment and population stratification appears crucial in assessing genetic modifiers in DMD. PMID:25641372

  4. The neuromuscular activity of Micrurus pyrrhocryptus venom and its neutralization by commercial and specific coral snake antivenoms

    PubMed Central

    Camargo, Thiago Magalhães; de Roodt, Adolfo Rafael; da Cruz-Höfling, Maria Alice; Rodrigues-Simioni, Léa

    2011-01-01

    The neuromuscular activity ofMicrurus pyrrochryptus venom was studied in chick biventer cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations. The venom (0.5-50μg/ml) caused irreversible, time- and concentration-dependent blockade, with BC being more sensitive than PND (50% blockade with 10μg/ml in 22±;3min and 62±4min, respectively; mean±SEM, n=6; p<0.05). In BC preparations, venom (0.5μg/ml) progressively abolished ACh-induced contractures, whereas contractures to exogenous KCl and muscle twitches in curarized preparations were unaffected. The venom neither altered creatine kinase release (venom: 25.8±1.75IU/l vs control: 24.3±2.2IU/l, n=6, after 120min), nor it caused significant muscle damage (50μg of venom/ml vs control: 3.5±0.8% vs 1.1±0.7% for PND; 4.3±1.5% vs 1.2±0.5% for BC, n=5). The venom had low PLA2 activity. Neurotoxicity was effectively neutralized by commercial Micrurus antivenom and specific antivenom. These findings indicate that M. pyrrhocryptus venom acts postsynaptically on nicotinic receptors, with no significant myotoxicity. PMID:21858249

  5. The neuromuscular activity of Micrurus pyrrhocryptus venom and its neutralization by commercial and specific coral snake antivenoms.

    PubMed

    Camargo, Thiago Magalhães; de Roodt, Adolfo Rafael; da Cruz-Höfling, Maria Alice; Rodrigues-Simioni, Léa

    2011-01-01

    The neuromuscular activity ofMicrurus pyrrochryptus venom was studied in chick biventer cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations. The venom (0.5-50μg/ml) caused irreversible, time- and concentration-dependent blockade, with BC being more sensitive than PND (50% blockade with 10μg/ml in 22±;3min and 62±4min, respectively; mean±SEM, n=6; p<0.05). In BC preparations, venom (0.5μg/ml) progressively abolished ACh-induced contractures, whereas contractures to exogenous KCl and muscle twitches in curarized preparations were unaffected. The venom neither altered creatine kinase release (venom: 25.8±1.75IU/l vs control: 24.3±2.2IU/l, n=6, after 120min), nor it caused significant muscle damage (50μg of venom/ml vs control: 3.5±0.8% vs 1.1±0.7% for PND; 4.3±1.5% vs 1.2±0.5% for BC, n=5). The venom had low PLA(2) activity. Neurotoxicity was effectively neutralized by commercial Micrurus antivenom and specific antivenom. These findings indicate that M. pyrrhocryptus venom acts postsynaptically on nicotinic receptors, with no significant myotoxicity. PMID:21858249

  6. Neuromuscular performance and bone structural characteristics in young healthy men and women.

    PubMed

    Rantalainen, T; Heinonen, A; Komi, P V; Linnamo, V

    2008-01-01

    Muscle mass and strength have been shown to be important factors in bone strength. Low muscular force predisposes to falling especially among elderly. Regular exercise helps to prevent falls and resulting bone fractures. Better understanding of muscle function and its importance on bone properties may thus add information to fracture prevention. Therefore the purpose of this study was to examine the relationship between bone strength and muscular force production. Twenty-young men [24 (2) years] and 20 [24 (3) years] women served as subjects. Bone compressive (BSI(d)) and bending strength indices (50 Imax) were measured with peripheral quantitative computed tomography (pQCT) at tibial mid-shaft and at distal tibia. Ankle plantarflexor muscle volume (MV) was estimated from muscle thickness measured with ultrasonography. Neuromuscular performance was evaluated from the measurements of maximal ground reaction force (GRF) in bilateral jumping and of eccentric maximal voluntary ankle plantarflexor torque (MVC). Specific tension (ST) of the plantarflexors was calculated by dividing the MVC with the muscle volume. Activation level (AL) was measured with superimposed twitch method. Distal tibia BSI(d) and tibial mid-shaft 50 Imax correlated positively with GRF, MVC and MV in men (r = 0.45-0.67, P < 0.05). Tibial mid-shaft 50 Imax and neuromuscular performance variables were correlated in women (r = 0.46-0.59, P < 0.05), whereas no correlation was seen in distal tibia. In the regression analysis, MV and ST could explain 64% of the variance in tibial mid-shaft bone strength and 41% of the variation in distal tibia bone strength. The study emphasizes that tibial strength is related to maximal neuromuscular performance. In addition, tibial mid-shaft seems to be more dependent on the neuromuscular performance, than distal tibia. In young adults, the association between bone adaptation and neuromuscular performance seems to be moderate and also site and loading specific.

  7. A Place for Block Play.

    ERIC Educational Resources Information Center

    Moore, Gary T.

    1997-01-01

    Discusses the importance of block play--including its contributions to perceptual, fine motor, and cognitive development--and components of a good preschool block play area. Recommends unit blocks complemented by stacking blocks, toys, beads, cubes, and Brio wooden toys. Makes recommendations for space, size, locations and connections to other…

  8. Inhibitory system overstimulation plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis

    PubMed Central

    Tuk, Bert

    2016-01-01

    Based upon a thorough review of published clinical observations regarding the inhibitory system, I hypothesize that this system may play a key role in the pathogenesis of a variety of neuromuscular and neurological diseases. Specifically, excitatory overstimulation, which is commonly reported in neuromuscular and neurological diseases, may be a homeostatic response to inhibitory overstimulation. Involvement of the inhibitory system in disease pathogenesis is highly relevant, given that most approaches currently being developed for treating neuromuscular and neurological diseases focus on reducing excitatory activity rather than reducing inhibitory activity. PMID:27547379

  9. Overstimulation of the inhibitory nervous system plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis

    PubMed Central

    Tuk, Bert

    2016-01-01

    Based upon a thorough review of published clinical observations regarding the inhibitory system, I hypothesize that this system may play a key role in the pathogenesis of a variety of neuromuscular and neurological diseases. Specifically, excitatory overstimulation, which is commonly reported in neuromuscular and neurological diseases, may be a homeostatic response to inhibitory overstimulation. Involvement of the inhibitory system in disease pathogenesis is highly relevant, given that most approaches currently being developed for treating neuromuscular and neurological diseases focus on reducing excitatory activity rather than reducing inhibitory activity. PMID:27547379

  10. A Fluid Block Schedule

    ERIC Educational Resources Information Center

    Ubben, Gerald C.

    1976-01-01

    Achieving flexibility without losing student accountability is a challenge that faces every school. With a fluid block schedule, as described here, accountability is maintained without inhibiting flexibility. An additional advantage is that three levels of schedule decision making take some of the pressure off the principal. (Editor)

  11. Spice Blocks Melanoma Growth

    ERIC Educational Resources Information Center

    Science Teacher, 2005

    2005-01-01

    Curcumin, the pungent yellow spice found in both turmeric and curry powders, blocks a key biological pathway needed for development of melanoma and other cancers, according to a study that appears in the journal Cancer. Researchers from The University of Texas M. D. Anderson Cancer Center demonstrate how curcumin stops laboratory strains of…

  12. Flattening basic blocks.

    SciTech Connect

    Utke, J.; Mathematics and Computer Science

    2006-01-01

    The application of cross country elimination strategies requires access to the computational graph or at least subgraphs for certain scopes, e.g. a basic block. Under the presence of aliased variables the construction of these (sub)graphs encounters ambiguities. We propose an algorithm to construct ambiguity free subgraphs.

  13. Ischemic Nerve Block.

    ERIC Educational Resources Information Center

    Williams, Ian D.

    This experiment investigated the capability for movement and muscle spindle function at successive stages during the development of ischemic nerve block (INB) by pressure cuff. Two male subjects were observed under six randomly ordered conditions. The duration of index finger oscillation to exhaustion, paced at 1.2Hz., was observed on separate…

  14. What's behind Block Scheduling?

    ERIC Educational Resources Information Center

    Gierke, Carolyn

    1999-01-01

    Discussion of block scheduling in secondary schools focuses on its impact on the school library media center. Discusses increased demand for library services, scheduling classes, the impact on librarians' time, teaching information technology, local area networks, and the increased pace of activity. (LRW)

  15. Acute effects of a dopamine/norepinephrine reuptake inhibitor on neuromuscular performance following self-paced exercise in cool and hot environments.

    PubMed

    Onus, Katrina; Cannon, Jack; Liberts, Liz; Marino, Frank E

    2016-08-01

    Dopamine/norepinephrine (DA/NE) reuptake inhibitors have been used to manipulate the central mechanisms affecting arousal and motivation during exercise. Eight healthy, physically active males performed 30min fixed-intensity cycling at 50% Wmax followed by 30min of self paced time trial (TT) with each section interspersed with a 30 s maximal sprint at 9, 19 and 29min. The DA/NE re-uptake inhibitor administered was bupropion (BUP) versus a placebo (PLA) in either warm (32°C, BUP32 or PLA32) or moderate (20°C; BUP20, PLA20) ambient conditions. Core and skin temperature, heart rate and perceptual responses, neuromuscular and hormonal measures were assessed at multiple times throughout the trials and post exercise. Time trial performance remained unchanged across conditions (12.7-13.1km) although core temperature was elevated in the fixed intensity section of the trials for BUP32 and BUP20 but continued to rise only in BUP32 during the time trial reaching 38.6°C (P<0.05). NE increased in all conditions from pre-exercise with BUP32 values peaking at the end of TT to 1245.3±203.1pg/mL (P<0.05) compared to the other conditions. Neuromuscular responses were similar among conditions although peak force was significantly reduced from pre (262±31N) to post (202±31N, P<0.05) exercise along with contraction duration (22%, P<0.05) in BUP20. We conclude that DA/NE re-uptake inhibitors influenced thermoregulation in the heat but not exercise performance. DA/NE re-uptake inhibitors are likely to act centrally to override the inhibitory signals for the cessation of exercise with these drugs acting peripherally to reduce the twitch characteristics of skeletal muscle in cooler conditions. PMID:27503717

  16. 24 CFR 570.614 - Architectural Barriers Act and the Americans with Disabilities Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DEVELOPMENT, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT COMMUNITY FACILITIES COMMUNITY DEVELOPMENT BLOCK... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Architectural Barriers Act and the Americans with Disabilities Act. 570.614 Section 570.614 Housing and Urban Development Regulations...

  17. Defects in Neuromuscular Transmission May Underlie Motor Dysfunction in Spinal and Bulbar Muscular Atrophy

    PubMed Central

    Xu, Youfen; Halievski, Katherine; Henley, Casey; Atchison, William D.; Katsuno, Masahisa; Adachi, Hiroaki; Sobue, Gen; Breedlove, S. Marc

    2016-01-01

    Spinal and bulbar muscular atrophy (SBMA) in men is an androgen-dependent neuromuscular disease caused by expanded CAG repeats in the androgen receptor (AR). Whether muscle or motor neuron dysfunction or both underlies motor impairment in SBMA is unknown. Muscles of SBMA mice show significant contractile dysfunction, implicating them as a likely source of motor dysfunction, but whether disease also impairs neuromuscular transmission is an open question. Thus, we examined synaptic function in three well-studied SBMA mouse models—the AR97Q, knock-in (KI), and myogenic141 models—by recording in vitro miniature and evoked end-plate potentials (MEPPs and EPPs, respectively) intracellularly from adult muscle fibers. We found striking defects in neuromuscular transmission suggesting that toxic AR in SBMA impairs both presynaptic and postsynaptic mechanisms. Notably, SBMA causes neuromuscular synapses to become weak and muscles to become hyperexcitable in all three models. Presynaptic defects included deficits in quantal content, reduced size of the readily releasable pool, and impaired short-term facilitation. Postsynaptic defects included prolonged decay times for both MEPPs and EPPs, marked resistance to μ-conotoxin (a sodium channel blocker), and enhanced membrane excitability. Quantitative PCR revealed robust upregulation of mRNAs encoding neonatal isoforms of the AChR (γ-subunit) and the voltage-gated sodium channel (NaV1.5) in diseased adult muscles of all three models, consistent with the observed slowing of synaptic potentials and resistance to μ-conotoxin. These findings suggest that muscles of SBMA patients regress to an immature state that impairs neuromuscular function. SIGNIFICANCE STATEMENT We have discovered that SBMA is accompanied by marked defects in neuromuscular synaptic transmission involving both presynaptic and postsynaptic mechanisms. For three different mouse models, we find that diseased synapses are weak, having reduced quantal content

  18. Architectural properties of the neuromuscular compartments in selected forearm skeletal muscles.

    PubMed

    Liu, An-Tang; Liu, Ben-Li; Lu, Li-Xuan; Chen, Gang; Yu, Da-Zhi; Zhu, Lie; Guo, Rong; Dang, Rui-Shan; Jiang, Hua

    2014-07-01

    The purposes f this study were to (i) explore the possibility of splitting the selected forearm muscles into separate compartments in human subjects; (ii) quantify the architectural properties of each neuromuscular compartment; and (iii) discuss the implication of these properties in split tendon transfer procedures. Twenty upper limbs from 10 fresh human cadavers were used in this study. Ten limbs of five cadavers were used for intramuscular nerve study by modified Sihler's staining technique, which confirmed the neuromuscular compartments. The other 10 limbs were included for architectural analysis of neuromuscular compartments. The architectural features of the compartments including muscle weight, muscle length, fiber length, pennation angle, and sarcomere length were determined. Physiological cross-sectional area and fiber length/muscle length ratio were calculated. Five of the selected forearm muscles were ideal candidates for splitting, including flexor carpi ulnaris, flexor carpi radials, extensor carpi radialis brevis, extensor carpi ulnaris and pronator teres. The humeral head of pronator teres contained the longest fiber length (6.23 ± 0.31 cm), and the radial compartment of extensor carpi ulnaris contained the shortest (2.90 ± 0.28 cm). The ulnar compartment of flexor carpi ulnaris had the largest physiological cross-sectional area (5.17 ± 0.59 cm(2)), and the ulnar head of pronator teres had the smallest (0.67 ± 0.06 cm(2)). Fiber length/muscle length ratios of the neuromuscular compartments were relatively low (average 0.27 ± 0.09, range 0.18-0.39) except for the ulnar head of pronator teres, which had the highest one (0.72 ± 0.05). Using modified Sihler's technique, this research demonstrated that each compartment of these selected forearm muscles has its own neurovascular supply after being split along its central tendon. Data of the architectural properties of each neuromuscular compartment provide insight into the 'design' of their

  19. Knee joint biomechanics and neuromuscular control during gait before and after total knee arthroplasty are sex-specific.

    PubMed

    Astephen Wilson, Janie L; Dunbar, Michael J; Hubley-Kozey, Cheryl L

    2015-01-01

    The future of total knee arthroplasty (TKA) surgery will involve planning that incorporates more patient-specific characteristics. Despite known biological, morphological, and functional differences between men and women, there has been little investigation into knee joint biomechanical and neuromuscular differences between men and women with osteoarthritis, and none that have examined sex-specific biomechanical and neuromuscular responses to TKA surgery. The objective of this study was to examine sex-associated differences in knee kinematics, kinetics and neuromuscular patterns during gait before and after TKA. Fifty-two patients with end-stage knee OA (28 women, 24 men) underwent gait and neuromuscular analysis within the week prior to and one year after surgery. A number of sex-specific differences were identified which suggest a different manifestation of end-stage knee OA between the sexes.

  20. An Integrated Approach to Change the Outcome Part II: Targeted Neuromuscular Training Techniques to Reduce Identified ACL Injury Risk Factors

    PubMed Central

    Myer, Gregory D.; Ford, Kevin R.; Brent, Jensen L.; Hewett, Timothy E.

    2014-01-01

    Prior reports indicate that female athletes who demonstrate high knee abduction moments (KAMs) during landing are more responsive to neuromuscular training designed to reduce KAM. Identification of female athletes who demonstrate high KAM, which accurately identifies those at risk for noncontact anterior cruciate ligament (ACL) injury, may be ideal for targeted neuromuscular training. Specific neuromuscular training targeted to the underlying biomechanical components that increase KAM may provide the most efficient and effective training strategy to reduce noncontact ACL injury risk. The purpose of the current commentary is to provide an integrative approach to identify and target mechanistic underpinnings to increased ACL injury in female athletes. Specific neuromuscular training techniques will be presented that address individual algorithm components related to high knee load landing patterns. If these integrated techniques are employed on a widespread basis, prevention strategies for noncontact ACL injury among young female athletes may prove both more effective and efficient. PMID:22580980

  1. Neuromuscular adaptations predict functional disability independently of clinical pain and psychological factors in patients with chronic non-specific low back pain.

    PubMed

    Dubois, Jean-Daniel; Abboud, Jacques; St-Pierre, Charles; Piché, Mathieu; Descarreaux, Martin

    2014-08-01

    Patients with chronic low back pain exhibit characteristics such as clinical pain, psychological symptoms and neuromuscular adaptations. The purpose of this study was to determine the independent contribution of clinical pain, psychological factors and neuromuscular adaptations to disability in patients with chronic low back pain. Clinical pain intensity, pain catastrophizing, fear-avoidance beliefs, anxiety, neuromuscular adaptations to chronic pain and neuromuscular responses to experimental pain were assessed in 52 patients with chronic low back pain. Lumbar muscle electromyographic activity was assessed during a flexion-extension task (flexion relaxation phenomenon) to assess both chronic neuromuscular adaptations and neuromuscular responses to experimental pain during the task. Multiple regressions showed that independent predictors of disability included neuromuscular adaptations to chronic pain (β=0.25, p=0.006, sr(2)=0.06), neuromuscular responses to experimental pain (β=-0.24, p=0.011, sr(2)=0.05), clinical pain intensity (β=0.28, p=0.002, sr(2)=0.08) and psychological factors (β=0.58, p<0.001, sr(2)=0.32). Together, these predictors accounted for 65% of variance in disability (R(2)=0.65 p<0.001). The current investigation revealed that neuromuscular adaptations are independent from clinical pain intensity and psychological factors, and contribute to inter-individual differences in patients' disability. This suggests that disability, in chronic low back pain patients, is determined by a combination of factors, including clinical pain, psychological factors and neuromuscular adaptations.

  2. The effect of temperature on the effects of the phospholipase A₂ neurotoxins β-bungarotoxin and taipoxin at the neuromuscular junction.

    PubMed

    Fathi, Behrooz; Harvey, Alan L; Rowan, Edward G

    2013-08-01

    Snake venom neurotoxins with phospholipase A₂ affect the neuromuscular junction with three distinct phases. There is a transient decrease in twitch height, followed by a facilitatory phase and finally a progressive blockade. It has been suggested that the initial phase is a direct consequence of the binding of the toxins to nerve terminals. This study was designed to determine whether the initial phase is present under conditions that would reduce the enzyme activity of the toxins. At 27 °C, β-bungarotoxin and taipoxin exhibited all three phases, i.e. 5-6 min after exposure to the preparation, twitch height was significantly reduced (P < 0.5) to 50 ± 4% and 64 ± 9% of control respectively. This was followed by facilitation and subsequent blockade. However, at 20 °C, neither toxin exhibited the first phase while the second phase, although reduced, clearly occurred and the blocking activity of these toxins always appeared. The data clearly demonstrate that the initial fall is temperature dependent as reducing the temperature from 27 °C to 20 °C blocks the first phase. As the second phase still occurs the toxins must have bound to their target. Therefore, the first phase cannot simply be a toxin binding step.

  3. Managing access block.

    PubMed

    Cameron, Peter; Scown, Paul; Campbell, Donald

    2002-01-01

    There is pessimism regarding the ability of the Acute Health Sector to manage access block for emergency and elective patients. Melbourne Health suffered an acute bed crisis in 2001 resulting in record ambulance diversions and emergency department (ED) delays. We conducted an observational study to reduce access block for emergency patients whilst maintaining elective throughput at Melbourne Health. This involved a clinician-led taskforce using previously proven principles for organisational change to implement 51 actions to improve patient access over a three-month period. The primary outcome measures were ambulance diversion, emergency patients waiting more than 12 hours for an inpatient bed, elective throughput and theatre cancellations. Despite a reduction in multi-day bed numbers all primary objectives were met, ambulance diversion decreased to minimal levels, 12-hour waits decreased by 40% and elective throughput was maintained. Theatre cancellations were also minimised. We conclude that access block can be improved by clinician-led implementation of proven process improvements over a short time frame. The ability to sustain change over the longer term requires further study.

  4. Block 3. This photograph depicts the northern view of Block ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Block 3. This photograph depicts the northern view of Block 2 towards the May D & F Tower from the main path along the western facades - Skyline Park, 1500-1800 Arapaho Street, Denver, Denver County, CO

  5. A quantitative description of tetanic and post-tetanic potentiation of transmitter release at the frog neuromuscular junction.

    PubMed

    Magleby, K L; Zengel, J E

    1975-02-01

    1. End-plate potential (e.p.p.s) were recorded with a surface electrode from frog neuromuscular junctions blocked with high Mg and low Ca to study post-tetanic potentiation (potentiation). 2. The magnitude of potentiation was not directly related to the number of conditioning impulses, but was a function of the frequency and duration of the conditioning stimulation. 3. Potentiation was always greater following an equal number of impulses delivered at a higher frequency of stimulation. 4. Plots of the magnitude of potentiation against the number of conditioning impulses would sometimes show an upward inflexion depending on the parameters of stimulation. 5. These experimental observations were described by a model based on the assumption (1) that potentiation is linearly related to a residual substance, R(t), which accumulates in the nerve terminal during repetitive stimulation, and (2) that each nerve impulse adds an identical increment, r, of this residual substance. The data were not described by assuming a 4th power relationship between potentiation and R(t). 6. The upward inflexion in potentiation (see paragraph 4) is described by the model as resulting from an increase in the time constant for the decay of potentiation as the magnitude of potentiation increases. 7. The increment of residual substance r added by each impulse was independent of the amount of transmitter released during the conditioning train. This increment typically increased transmitter release by amount 1% of the control level in the absence of potentiation. 8. Suggestions are given to explain why potentiation of transmitter release, which is thought to arise from an accumulation of Ca-2+ in the nerve terminal, can be described assuming a linear relationship between potentiation and R(t), the proposed substance responsible for potentiation, under experimental conditions in which a 3rd to 4th power relationship would be expected to exist between external Ca concentration and evoked transmitter

  6. The use of sugammadex for bariatric surgery: analysis of recovery time from neuromuscular blockade and possible economic impact

    PubMed Central

    De Robertis, Edoardo; Zito Marinosci, Geremia; Romano, Giovanni Marco; Piazza, Ornella; Iannuzzi, Michele; Cirillo, Fabrizio; De Simone, Stefania; Servillo, Giuseppe

    2016-01-01

    Background Neuromuscular block (NMB) monitoring and use of reversal agents accelerate the recovery time and improve the workflow in the operating room. We aimed to compare recovery times after sugammadex or neostigmine administration, and estimate the time spent in operating theater and the possible economic impact of a faster recovery, in morbidly obese patients undergoing bariatric surgery. Methods We conducted a retrospective study that analyzed data from records of morbidly obese patients (body mass index >40 kg/m2) undergoing elective laparoscopic bariatric surgery in which sugammadex or neostigmine were used to reverse NMB. Patients were divided in two groups: group 1 (sugammadex group [SUG]) received rocuronium and sugammadex for reversal and group 2 (neostigmine group [NEO]) received either rocuronium or cisatracurium and neostigmine. Data are presented as mean (standard deviation). Results Compared with NEO, SUG group showed shorter times to achieve train-of-four ratio of 0.9 (P<0.05) and an Aldrete score of 10 (P<0.05), a higher cost (€146.7 vs €3.6 [P<0.05]), plus a remarkable less duration of operating theater occupancy (P<0.05). Sugammadex cost accounted for 2.58% of the total cost per surgery, while neostigmine cost accounted for 0.06%. Total time saved in SUG group was 19.4 hours, which could be used to perform 12 extra laparoscopic sleeve gastrectomies. Conclusion Reversal from NMB was significantly faster with sugammadex than with neostigmine. Although sugammadex was substantially more expensive, duration of operating theater occupancy was reduced with potentially workflow increase or personnel reduced cost. PMID:27418846

  7. A study of tetanic and post-tetanic potentiation of miniature end-plate potentials at the frog neuromuscular junction.

    PubMed Central

    Lev-Tov, A; Rahamimoff, R

    1980-01-01

    1. The involvement of calcium sodium, potassium and magnesium in tetanic and post-tetanic potentiation of miniature end-plate potential frequency was examined at the frog neuromuscular junction using conventional electrophysiological techniques. 2. Tetanic potentiation is larger in calcium containing solutions, than in solutions which generate reversed electrochemical gradient for calcium during nerve activity. 3. Tetanic potentiation increases with stimulation frequency and duration, under both inward and reversed electrochemical gradient for calcium conditions. This indicates that factors, other than calcium entry, participate in tetanic potentiation. 4. Addition of the potassium conductance blocking agent, 3-aminopyridine (5 mM), increases tetanic potentiation in calcium containing media, while depressing it under reversed calcium gradient. 5. Electronic depolarization of the nerve terminal in tetrodotoxin-containing Ringer solution, produces tetanic potentiation under inward gradient, but fails to do so under reversed gradient. This indicates that the entry of sodium ions participates in the generation of tetanic potentiation. 6. Addition of magnesium ions suppresses tetanic potentiation in calcium containing solution, but increases tetanic potentiation under reversed gradient. 7. The results are explained by the hypothesis that calcium entry and intracellular calcium translocation participate in the generation of tetanic potentiation. 8. Both the fast and the slow components (augmentation and potentiation respectively) of post-tetanic potentiation increase in duration, with increase in the tetanic stimulation rate. 9. The decay of post-tetanic potentiation increases: when [Ca]o is elevated by ionophoretic application during the decay phase only, when ouabain is present in the medium or when [Mg]o is elevated. These finding suggest that calcium, sodium and possibly magnesium take part in post-tetanic potentiation. PMID:6973021

  8. Block Transfer Handbook: Constructing and Negotiating Block Transfer Agreements.

    ERIC Educational Resources Information Center

    Finlay, Finola

    The purpose of this handbook is to provide resources for institutions or articulation committees who are engaged in the task of investigating the feasibility of block transfer agreements. Block transfer is the process whereby a block of credits is granted to students who have successfully completed a certificate, diploma, or cluster of courses…

  9. View southeast of caps for blocks for JFK; blocks are ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View southeast of caps for blocks for JFK; blocks are used to support ship when it is repositioned to paint inaccessible areas masked by original support blocks. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Carpentry Shop, League Island, Philadelphia, Philadelphia County, PA

  10. Enhancement of Neuromuscular Activity by Natural Specimens and Cultured Mycelia of Cordyceps sinensis in Mice.

    PubMed

    Singh, K P; Meena, H S; Negi, P S

    2014-09-01

    The present study was aimed to evaluate the effect of natural specimen and laboratory cultured mycelia of Cordyceps sinensis on neuromuscular activity in mice. The powder of natural specimen and laboratory cultured Cordyceps sinensis was orally administered at the dose rate of 100, 300 and 500 mg/kg for 30 days. Natural specimen and in vitro propagated Cordyceps sinensis showed significant (P<0.05) enhancement in neuromuscular endurance and antidepressant activity at 300 and 500 mg/kg as compared to the control group. However, the fungus did not proved to be as effective as fluoxetine in exhibiting antidepressant action. Muscular endurance was determined on a Rota rod apparatus while antidepressant (mood elevating) activity was measured on a photoactometer in Swiss albino mice. The effects produced by both natural specimens and laboratory cultured Cordyceps sinensis were comparable and showed almost equal potency.

  11. The use of "stabilization exercises" to affect neuromuscular control in the lumbopelvic region: a narrative review.

    PubMed

    Bruno, Paul

    2014-06-01

    It is well-established that the coordination of muscular activity in the lumbopelvic region is vital to the generation of mechanical spinal stability. Several models illustrating mechanisms by which dysfunctional neuromuscular control strategies may serve as a cause and/or effect of low back pain have been described in the literature. The term "core stability" is variously used by clinicians and researchers, and this variety has led to several rehabilitative approaches suggested to affect the neuromuscular control strategies of the lumbopelvic region (e.g. "stabilization exercise", "motor control exercise"). This narrative review will highlight: 1) the ongoing debate in the clinical and research communities regarding the terms "core stability" and "stabilization exercise", 2) the importance of sub-grouping in identifying those patients most likely to benefit from such therapeutic interventions, and 3) two protocols that can assist clinicians in this process.

  12. [Neuromuscular dynamic scapular winging: Clinical, electromyographic and magnetic resonance imaging diagnosis].

    PubMed

    Nguyen, Christelle; Guérini, Henri; Roren, Alexandra; Zauderer, Jennifer; Vuillemin, Valérie; Seror, Paul; Ouaknine, Michaël; Palazzo, Clémence; Bourdet, Christopher; Pluot, Étienne; Roby-Brami, Agnès; Drapé, Jean-Luc; Rannou, François; Poiraudeau, Serge; Lefèvre-Colau, Marie-Martine

    2015-12-01

    Dyskinesia of the scapula is a clinical diagnosis and includes all disorders affecting scapula positioning and movement whatever its etiology. Scapular winging is a subtype of scapular dyskinesia due to a dynamic prominence of the medial border of the scapula (DSW) secondary to neuromuscular imbalance in the scapulothoracic stabilizer muscles. The two most common causes of DSW are microtraumatic or idiopathic lesions of the long thoracic nerve (that innerves the serratus anterior) or the accessory nerve (that innerves the trapezius). Diagnosis of DSW is clinical and electromyographic. Use of magnetic resonance imaging (MRI) could be of interest to distinguish lesion secondary to a long thoracic nerve from accessory nerve and to rule out scapular dyskinesia related to other shoulder disorders. Causal neuromuscular lesion diagnosis in DSW is challenging. Clinical examinations, combined with scapular MRI, could help to their specific diagnosis, determining their stage, ruling out differential diagnosis and thus give raise to more targeted treatment. PMID:26433832

  13. CLINICAL APPROACH TO THE DIAGNOSTIC EVALUATION OF HERDITARY AND ACQUIRED NEUROMUSCULAR DISEASES

    PubMed Central

    McDonald, Craig M.

    2012-01-01

    SYNOPSIS In the context of a neuromuscular disease diagnostic evaluation, the clinician still must be able to obtain a relevant patient and family history and perform focused general, musculoskeletal, neurologic and functional physical examinations to direct further diagnostic evaluations. Laboratory studies for hereditary neuromuscular diseases include relevant molecular genetic studies. The EMG and nerve conduction studies remain an extension of the physical examination and help to guide further diagnostic studies such as molecular genetic studies, and muscle and nerve biopsies. All diagnostic information needs to be interpreted not in isolation, but within the context of relevant historical information, family history, physical examination findings, and laboratory data, electrophysiologic findings, pathologic findings, and molecular genetic findings if obtained. PMID:22938875

  14. Mixed cholinergic/glutamatergic neuromuscular innervation of Onychophora: a combined histochemical/electrophysiological study.

    PubMed

    Stern, Michael; Bicker, Gerd

    2008-08-01

    Morphological and molecular phylogenetic data show that the Onychophora are close relatives of the Arthropoda. However, onychophoran neuromuscular junctions have been reported to employ acetylcholine, as in annelids, nematodes, and other bilaterians, rather than glutamate, as in arthropods. Here, we show that the large longitudinal muscles of Peripatoides respond indeed only to acetylcholine, whereas the oblique and ring muscles of the body wall are sensitive both to acetylcholine and to L-glutamate. Moreover, cytochemical staining reveals both acetylcholinesterase- and glutamate-positive synaptic boutons on oblique and ring muscles. These novel findings agree with a phylogenetic position of onychophorans basal to that of the arthropods. Although the glutamatergic phenotype of excitatory neuromuscular transmission may be a characteristic feature of arthropods and present even in a subset of onychophoran motor neurons, the motor neurons of the longitudinal muscles still retain the cholinergic phenotype typical for annelids and other taxa. PMID:18563449

  15. [Neuromuscular dynamic scapular winging: Clinical, electromyographic and magnetic resonance imaging diagnosis].

    PubMed

    Nguyen, Christelle; Guérini, Henri; Roren, Alexandra; Zauderer, Jennifer; Vuillemin, Valérie; Seror, Paul; Ouaknine, Michaël; Palazzo, Clémence; Bourdet, Christopher; Pluot, Étienne; Roby-Brami, Agnès; Drapé, Jean-Luc; Rannou, François; Poiraudeau, Serge; Lefèvre-Colau, Marie-Martine

    2015-12-01

    Dyskinesia of the scapula is a clinical diagnosis and includes all disorders affecting scapula positioning and movement whatever its etiology. Scapular winging is a subtype of scapular dyskinesia due to a dynamic prominence of the medial border of the scapula (DSW) secondary to neuromuscular imbalance in the scapulothoracic stabilizer muscles. The two most common causes of DSW are microtraumatic or idiopathic lesions of the long thoracic nerve (that innerves the serratus anterior) or the accessory nerve (that innerves the trapezius). Diagnosis of DSW is clinical and electromyographic. Use of magnetic resonance imaging (MRI) could be of interest to distinguish lesion secondary to a long thoracic nerve from accessory nerve and to rule out scapular dyskinesia related to other shoulder disorders. Causal neuromuscular lesion diagnosis in DSW is challenging. Clinical examinations, combined with scapular MRI, could help to their specific diagnosis, determining their stage, ruling out differential diagnosis and thus give raise to more targeted treatment.

  16. Loss of motoneuron-specific microRNA-218 causes systemic neuromuscular failure.

    PubMed

    Amin, Neal D; Bai, Ge; Klug, Jason R; Bonanomi, Dario; Pankratz, Matthew T; Gifford, Wesley D; Hinckley, Christopher A; Sternfeld, Matthew J; Driscoll, Shawn P; Dominguez, Bertha; Lee, Kuo-Fen; Jin, Xin; Pfaff, Samuel L

    2015-12-18

    Dysfunction of microRNA (miRNA) metabolism is thought to underlie diseases affecting motoneurons. One miRNA, miR-218, is abundantly and selectively expressed by developing and mature motoneurons. Here we show that mutant mice lacking miR-218 die neonatally and exhibit neuromuscular junction defects, motoneuron hyperexcitability, and progressive motoneuron cell loss, all of which are hallmarks of motoneuron diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. Gene profiling reveals that miR-218 modestly represses a cohort of hundreds of genes that are neuronally enriched but are not specific to a single neuron subpopulation. Thus, the set of messenger RNAs targeted by miR-218, designated TARGET(218), defines a neuronal gene network that is selectively tuned down in motoneurons to prevent neuromuscular failure and neurodegeneration.

  17. Neuromuscular Junctions as Key Contributors and Therapeutic Targets in Spinal Muscular Atrophy

    PubMed Central

    Boido, Marina; Vercelli, Alessandro

    2016-01-01

    Spinal muscular atrophy (SMA) is a recessive autosomal neuromuscular disease, representing the most common fatal pediatric pathology. Even though, classically and in a simplistic way, it is categorized as a motor neuron (MN) disease, there is an increasing general consensus that its pathogenesis is more complex than expected. In particular, neuromuscular junctions (NMJs) are affected by dramatic alterations, including immaturity, denervation and neurofilament accumulation, associated to impaired synaptic functions: these abnormalities may in turn have a detrimental effect on MN survival. Here, we provide a description of NMJ development/maintenance/maturation in physiological conditions and in SMA, focusing on pivotal molecules and on the time-course of pathological events. Moreover, since NMJs could represent an important target to be exploited for counteracting the pathology progression, we also describe several therapeutic strategies that, directly or indirectly, aim at NMJs. PMID:26869891

  18. Increased Asynchronous Release and Aberrant Calcium Channel Activation in Amyloid Precursor Protein Deficient Neuromuscular Synapses

    PubMed Central

    Yang, Li; Wang, Baiping; Long, Cheng; Wu, Gangyi; Zheng, Hui

    2007-01-01

    Despite the critical roles of the amyloid precursor protein (APP) in Alzheimer's disease pathogenesis, its physiological function remains poorly established. Our previous studies implicated a structural and functional activity of the APP family of proteins in the developing neuromuscular junction (NMJ). Here we performed comprehensive analyses of neurotransmission in mature neuromuscular synapse of APP deficient mice. We found that APP deletion led to reduced paired-pulse facilitation and increased depression of synaptic transmission with repetitive stimulation. Readily releasable pool size and total releasable vesicles were not affected, but probability of release was significantly increased. Strikingly, the amount of asynchronous release, a measure sensitive to presynaptic calcium concentration, was dramatically increased, and pharmacological studies revealed that it was attributed to aberrant activation of N- and L-type Ca2+ channels. We propose that APP modulates synaptic transmission at the NMJ by ensuring proper Ca2+ channel function. PMID:17919826

  19. Resistance training improves capacity to delay neuromuscular fatigue in older adults.

    PubMed

    Emerson, Nadia S; Stout, Jeffrey R; Fukuda, David H; Robinson, Edward H; Iv; Scanlon, Tyler C; Beyer, Kyle S; Fragala, Maren S; Hoffman, Jay R

    2015-01-01

    The purpose of this study was to investigate the effects of short term resistance exercise on neuromuscular fatigue threshold (PWCFT), strength, functional performance, and body composition in older adults. Twenty-three participants (71.2 ± 6.0 yr) were randomly assigned to 6 weeks of resistance exercise (EXE) or control (CONT). A submaximal cycle ergometer test, physical working capacity at fatigue threshold, was used to determine PWCFT. Strength was assessed with predicted leg extension 1-RM and functional performance with time to complete 5 chair rises (CHAIR) and walk an 8-ft course (WALK). PWCFT, 1-RM and CHAIR significantly (p<0.05) improved in the EXE (27%, 24%, 27%) compared with CONT (-0.1%, 7%, 6%), respectively. The results of this study suggest that short term EXE improved strength, functionality and the capacity to delay the onset of neuromuscular fatigue in older adults.

  20. Mixed cholinergic/glutamatergic neuromuscular innervation of Onychophora: a combined histochemical/electrophysiological study.

    PubMed

    Stern, Michael; Bicker, Gerd

    2008-08-01

    Morphological and molecular phylogenetic data show that the Onychophora are close relatives of the Arthropoda. However, onychophoran neuromuscular junctions have been reported to employ acetylcholine, as in annelids, nematodes, and other bilaterians, rather than glutamate, as in arthropods. Here, we show that the large longitudinal muscles of Peripatoides respond indeed only to acetylcholine, whereas the oblique and ring muscles of the body wall are sensitive both to acetylcholine and to L-glutamate. Moreover, cytochemical staining reveals both acetylcholinesterase- and glutamate-positive synaptic boutons on oblique and ring muscles. These novel findings agree with a phylogenetic position of onychophorans basal to that of the arthropods. Although the glutamatergic phenotype of excitatory neuromuscular transmission may be a characteristic feature of arthropods and present even in a subset of onychophoran motor neurons, the motor neurons of the longitudinal muscles still retain the cholinergic phenotype typical for annelids and other taxa.

  1. The immediate effect of lumbar spine patterns of neuromuscular joint facilitation in young amateur baseball players.

    PubMed

    Huo, Ming; Maruyama, Hitoshi; Kaneko, Takasumi; Naito, Daiki; Koiso, Yuta

    2013-12-01

    [Purpose] The aim of the study was to investigate the changes in baseball pitching velocity, the functional reach test (FR) and the simple reaction times (SRT) in young amateur baseball players after lumbar spine patterns of neuromuscular joint facilitation (NJF) treatment. [Subjects] The subjects were 11 young amateur baseball players. An NJF intervention and a proprioceptive neuromuscular facilitation (PNF) intervention were performed. The interventions were performed one after the other with one week between them. The order of the interventions was completely randomized. [Methods] The baseball pitching velocity, the FR and the SRT were evaluated before and after treatment. [Results] In the NJF group, there were significant differences in baseball pitching velocity, FR and SRT after treatment. In the PNF group, there was a significant difference in SRT after treatment. [Conclusion] NJF intervention shortens the SRT, increases the baseball pitching velocity and FR, and may be recommended to improve performance in baseball players. PMID:24409011

  2. The immediate effect of lumbar spine patterns of neuromuscular joint facilitation in young amateur baseball players.

    PubMed

    Huo, Ming; Maruyama, Hitoshi; Kaneko, Takasumi; Naito, Daiki; Koiso, Yuta

    2013-12-01

    [Purpose] The aim of the study was to investigate the changes in baseball pitching velocity, the functional reach test (FR) and the simple reaction times (SRT) in young amateur baseball players after lumbar spine patterns of neuromuscular joint facilitation (NJF) treatment. [Subjects] The subjects were 11 young amateur baseball players. An NJF intervention and a proprioceptive neuromuscular facilitation (PNF) intervention were performed. The interventions were performed one after the other with one week between them. The order of the interventions was completely randomized. [Methods] The baseball pitching velocity, the FR and the SRT were evaluated before and after treatment. [Results] In the NJF group, there were significant differences in baseball pitching velocity, FR and SRT after treatment. In the PNF group, there was a significant difference in SRT after treatment. [Conclusion] NJF intervention shortens the SRT, increases the baseball pitching velocity and FR, and may be recommended to improve performance in baseball players.

  3. [A new neuromuscular transmission monitor (TOF Guard): the rationale behind the method and its clinical usefulness].

    PubMed

    Ueda, N; Masuda, Y; Muteki, T; Tsuda, H; Hiraki, T; Harada, H; Tobata, H

    1994-01-01

    TOF Guard is one of the latest developments in the field of neuromuscular monitoring equipment. This system uses a miniature acceleration transducer (a piezo-electric ceramic wafer is used), simply fastened to the thumb with tape. The rationale behind the method is Newton's second law, stating that the acceleration is directly proportional to the force. In this study, authors assessed the accuracy of this system in clinical use, comparing with the force transducer method (Myograph 2000). The result showed that there was a very close positive correlation between the values of T1, TOF ratio and posttetanic count simultaneously measured by both methods. The coefficient of correlation was 0.96, and its significance level was P < 0.001. From the clinical view point, it is concluded that TOF Guard is very useful because of its accuracy and because the equipment is easy to handle, compact and of low price as a neuromuscular monitoring system for routine anesthesia.

  4. Neuromuscular Activity of Upper and Lower Limbs during two Backstroke Swimming Start Variants.

    PubMed

    De Jesus, Karla; De Jesus, Kelly; Medeiros, Alexandre I A; Gonçalves, Pedro; Figueiredo, Pedro; Fernandes, Ricardo J; Vilas-Boas, João Paulo

    2015-09-01

    swimmers' vertex reaches the 15 m mark) is decisive in short distance events.In 2008, FINA approved the Omega OSB11 starting block (Swiss Timing Ltd., Switzerland) with two horizontal and one vertical backstroke start handgrip and currently swimmers can adopt different starting variants.The start performance is related to the exertion of maximal force in the shortest time, as other high-velocity movements; thus, the study of the current variants in-between them from a neuromuscular standpoint is indispensable for training support.The use of different handgrips did not affect upper and lower limb electromyographic activity; angular kinematics and overall 15 m backstroke start profile.Independent of the start variant selected, the role played by each upper and lower limb muscles at different starting phases should be considered in specific resistance training program to optimize backstroke start performance. PMID:26336346

  5. Neuromuscular Activity of Upper and Lower Limbs during two Backstroke Swimming Start Variants

    PubMed Central

    De Jesus, Karla; De Jesus, Kelly; Medeiros, Alexandre I. A.; Gonçalves, Pedro; Figueiredo, Pedro; Fernandes, Ricardo J.; Vilas-Boas, João Paulo

    2015-01-01

    swimmers’ vertex reaches the 15 m mark) is decisive in short distance events. In 2008, FINA approved the Omega OSB11 starting block (Swiss Timing Ltd., Switzerland) with two horizontal and one vertical backstroke start handgrip and currently swimmers can adopt different starting variants. The start performance is related to the exertion of maximal force in the shortest time, as other high-velocity movements; thus, the study of the current variants in-between them from a neuromuscular standpoint is indispensable for training support. The use of different handgrips did not affect upper and lower limb electromyographic activity; angular kinematics and overall 15 m backstroke start profile. Independent of the start variant selected, the role played by each upper and lower limb muscles at different starting phases should be considered in specific resistance training program to optimize backstroke start performance. PMID:26336346

  6. Block Copolymer Templates for Optical Materials and Devices

    NASA Astrophysics Data System (ADS)

    Urbas, Augustine; Martin, Maldovan; Carter, W. C.; Thomas, E. L.; Fasolka, Michael; Fraser, Cassandra

    2002-03-01

    Block copolymers can act as super-lattices for creating novel optical structures. We have fabricated block copolymer photonic crystals from one, two and three dimensionally periodic systems and have enhanced their dielectric properties towards creating complete 3D band gaps. By using carefully selected blends of linear and star block copolymers, we are able to create hierarchical blends which exhibit precise molecular positioning of fluorescent molecules. We are exploring these unique patterning capabilities of block copolymer systems for the formation of ordered arrays of optically active components within a photonic crystal. Precise location of both fluorescent and nonlinear components within block copolymer photonic crystals affords new opportunities for creating low threshold, upconverting and array lasers as well as optical modulators and other photonic devices.

  7. The poor man's cell block

    PubMed Central

    Darlington, Ann

    2010-01-01

    The authors describe a simple method for making formalin or isopropyl alcohol vapour fixed cell blocks from fine needle aspiration cytology specimens that we refer to as ‘The Poor Man's Cell Block.’ PMID:20671053

  8. Effects of Short- and Long-Duration Space Flight on Neuromuscular Function

    NASA Technical Reports Server (NTRS)

    Buxton, Roxanne E.; Spiering, Barry A.; Ryder, Jeffrey W.; Ploutz-Snyder, Lori L.; Bloomberg, Jacob J.

    2010-01-01

    The Functional Task Tests (FTT) is an interdisciplinary study designed to correlate the changes in functional tasks (such as emergency egress, ladder climbing, and hatch opening) with changes in neuromuscular, cardiovascular, and sensorimotor function. One aspect of the FTT, the neuromuscular function test, is used to investigate the neuromuscular component underlying changes in the ability of astronauts to perform functional tasks (representative of critical mission tasks) safely and quickly after flight. PURPOSE: To describe neuromuscular function after short- and long-duration space flight. METHODS: To date, 5 crewmembers on short-duration (10- to 15-day) missions and 3 on long-duration missions have participated. Crewmembers were assessed 30 days before flight, on landing day (short-duration subjects only) and 1, 6, and 30 days after landing. The interpolated twitch technique, which utilizes a combination of maximal voluntary contractions and electrically evoked contractions, was used to assess the maximal voluntary isometric force (MIF) and central activation capacity of the knee extensors. Leg-press and bench-press devices were used to assess MIF and maximal dynamic power of the lower and upper body respectively. Specifically, power was measured during concentric-only ballistic throws of the leg-press sled and bench-press bar loaded to 40% and 30% of MIF respectively. RESULTS: Data are currently being collected from both Shuttle and ISS crewmembers. Emerging data indicate that measures of knee extensor muscle function are decreased with long-duration flight. DISCUSSION: The relationships between flight duration, neural drive, and muscle performance are of particular interest. Ongoing research will add to the current sample size and will focus on defining changes in muscle performance measures after long-duration space flight.

  9. [Muscle relaxants and neuromuscular monitoring - Introduction for a safe clinical application].

    PubMed

    Döcker, Dennis; Walther, Andreas

    2012-05-01

    The use of muscle relaxants facilitates endotracheal intubation and ameliorates the conditions of surgery. But, their use should be controlled - otherwise there will be postoperative residual curarisation which can lead to patient discomfort up to severe medical complications. Therefore, an appropriate surveillance via objective neuromuscular monitoring is essential. This article gives a review of the basic principles of muscle relaxants, their clinical application and the surveillance of their effects and degradation.

  10. [Muscle relaxants and neuromuscular monitoring - Introduction for a safe clinical application].

    PubMed

    Döcker, Dennis; Walther, Andreas

    2012-05-01

    The use of muscle relaxants facilitates endotracheal intubation and ameliorates the conditions of surgery. But, their use should be controlled - otherwise there will be postoperative residual curarisation which can lead to patient discomfort up to severe medical complications. Therefore, an appropriate surveillance via objective neuromuscular monitoring is essential. This article gives a review of the basic principles of muscle relaxants, their clinical application and the surveillance of their effects and degradation. PMID:22628025

  11. Reactive Neuromuscular Training for the Anterior Cruciate Ligament-Deficient Knee: A Case Report

    PubMed Central

    Cook, Gray; Burton, Lee; Fields, Keith

    1999-01-01

    Objective: To demonstrate the response to a proprioceptive training model during a 1-week rehabilitation regime. The techniques were demonstrated on a college-aged female basketball player who had injured her anterior cruciate ligament (ACL) several weeks earlier. The athlete was tested, trained, and then retested during her semester break. Background: The ACL injury has become a fairly common occurrence in the world of athletics. Knowing this, the athletic trainer is constantly searching for ways to improve the rehabilitative process. New research demonstrates that rehabilitation should be based on proprioception. The ACL not only serves a mechanical role by limiting passive knee mobility but also serves a sensory role through the mechanoreceptors deep in its tissue, which communicate with the neuromuscular system to provide proprioceptive feedback during training and competition. Differential Diagnosis: Partial or complete tear of the ACL. Treatment: The athlete was treated with a rehabilitation protocol based on proprioception, which uses reactive neuromuscular training. Uniqueness: Our rehabilitation focused on the muscular imbalances about the hip, knee, and ankle. The athlete achieved dramatic decreases in muscular imbalances about the hip and knee in only 1 week of rehabilitation through reactive neuromuscular training. Conclusions: The athlete had significant gains in strength over her brief period of therapy. However, these gains can be viewed only as neuromuscular changes and not strictly as gains in strength. The athlete returned to postseason competition under the supervision of her surgeon, who later recommended surgical reconstruction at the completion of the basketball season with rehabilitation during the offseason. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6.Figure 7.Figure 8.Figure 9.Figure 10.Figure 11.Figure 12. PMID:16558562

  12. Single leg jumping neuromuscular control is improved following whole body, long-axis rotational training.

    PubMed

    Nyland, John; Burden, Robert; Krupp, Ryan; Caborn, David N M

    2011-04-01

    Improved lower extremity neuromuscular control during sports may decrease injury risk. This prospective study evaluated progressive resistance, whole body, long-axis rotational training on the Ground Force 360 device. Our hypothesis was that device training would improve lower extremity neuromuscular control based on previous reports of kinematic, ground reaction force (GRF) or electromyographic (EMG) evidence of safer or more efficient dynamic knee stability during jumping. Thirty-six healthy subjects were randomly assigned to either training (Group 1) or control (Group 2) groups. Using a pre-test, post-test study design data were collected from three SLVJ trials. Unpaired t-tests with adjustments for multiple comparisons were used to evaluate group mean change differences (P≤0.05/25≤0.002). During propulsion Group 1 standardized EMG amplitude mean change differences for gluteus maximus (-21.8% vs. +17.4%), gluteus medius (-28.6% vs. +15.0%), rectus femoris (-27.1% vs. +11.2%), vastus medialis (-20.2% vs. +9.1%), and medial hamstrings (-38.3% vs. +30.3%) differed from Group 2. During landing Group 1 standardized EMG amplitude mean change differences for gluteus maximus (-32.9% vs. +11.1%) and rectus femoris (-33.3% vs. +29.0%) also differed from Group 2. Group 1 peak propulsion vertical GRF (+0.24N/kg vs. -0.46N/kg) and landing GRF stabilization timing (-0.68 vs. +0.05s) mean change differences differed from Group 2. Group 1 mean hip (-16.3 vs. +7.8°/s) and knee (-21.4 vs. +18.5°/s) flexion velocity mean change differences also differed from Group 2. Improved lower extremity neuromuscular efficiency, increased peak propulsive vertical GRF, decreased mean hip and knee flexion velocities during landing, and earlier landing stabilization timing in the training group suggests improved lower extremity neuromuscular control.

  13. Comparative investigation of the pharmacology of fish and mammalian neuromuscular systems

    SciTech Connect

    Gant, D.B.

    1985-01-01

    Neuromuscular pharmacology has been extensively studied in mammals but there have been few investigations examining the neuromuscular systems of fish. In situ experiments have shown that the basic cholinergic characteristics of fish neuromuscular junctions are different from those of mammals. In order to further understand the nature of these differences, the nicotinic acetylcholine receptors (AChR) of rat and buffalo sculpin (Enophrys bison) neuromuscular junctions and the AChR of electric ray (Torpedo california) electroplax, were investigated using receptor binding analysis. A rapid filtration assay was utilized to measure (/sup 125/I)..cap alpha..-BGT binding to tissue membranes. Scatchard analysis of (/sup 175/I)..cap alpha..-BGT binding was performed on sculpin pectoral muscle rat gastrocnemius, rat denervated gastrocnemius, and Torpedo electroplax. The affinity constant was similar for all tissues studied. In competition studies, d-tubocurarine had the highest affinity for the (/sup 125/I)-..cap alpha..-BGT binding site in all tissues, illustrating the nicotinic nature of the binding sites. Acetylcholine had high affinity for the rat gastrocnemius binding site and low affinity for the sculpin pectoral muscle and Torpedo electroplax binding site. Atropine had high affinity for the sculpin pectoral muscle binding site when compared to the rate gastrocnemius and Torpedo electroplax binding site, indicating that the sculpin pectoral site may have some mixed muscarinic-nicitinic characteristics. These results indicate that there are definite qualitative as well as quantitative differences between the fish skeletal muscle nicotinic receptor and the nicotinic receptor of fish electroplax and rat skeletal muscle.

  14. Test battery designed to quickly and safely assess diverse indices of neuromuscular function after unweighting.

    PubMed

    Spiering, Barry A; Lee, Stuart M C; Mulavara, Ajitkumar P; Bentley, Jason R; Buxton, Roxanne E; Lawrence, Emily L; Sinka, Joseph; Guilliams, Mark E; Ploutz-Snyder, Lori L; Bloomberg, Jacob J

    2011-02-01

    Adequately describing the functional consequences of unweighting (e.g., bed rest, immobilization, spaceflight) requires assessing diverse indices of neuromuscular function (i.e., strength, power, endurance, central activation, force steadiness). Additionally, because unweighting increases the susceptibility of muscle to damage, testing should consider supplementary safety features. The purpose of this study was to develop a test battery for quickly assessing diverse indices of neuromuscular function. Commercially available exercise equipment was modified to include data acquisition hardware (e.g., force plates, position transducers) and auxiliary safety hardware (e.g., magnetic brakes). Ten healthy, ambulatory subjects (31 ± 5 years, 173 ± 11 cm, 73 ± 14 kg) completed a battery of lower- and upper-body neuromuscular function tests on 3 occasions separated by at least 48 hours. The battery consisted of the following tests, in order: (1) knee extension central activation, (2) knee extension force steadiness, (3) leg press maximal strength, (4) leg press maximal power, (5) leg press power endurance, (6) bench press maximal strength, (7) bench press force steadiness, (8) bench press maximal power, and (9) bench press power endurance. Central activation, strength, rate of force development, maximal power, and power endurance (total work) demonstrated good-to-excellent measurement reliability (SEM = 3-14%; intraclass correlation coefficient [ICC] = 0.87-0.99). The SEM of the force steadiness variables was 20-35% (ICC = 0.20-0.60). After familiarization, the test battery required 49 ± 6 minutes to complete. In conclusion, we successfully developed a test battery that could be used to quickly and reliably assess diverse indices of neuromuscular function. Because the test battery involves minimal eccentric muscle actions and impact forces, the potential for muscle injury has likely been reduced.

  15. HIV-related neuromuscular diseases: nemaline myopathy, amyotrophic lateral sclerosis and bibrachial amyotrophic diplegia.

    PubMed

    Rowland, L P

    2011-06-01

    The human immunodeficiency virus (HIV) causes diverse disorders of the brain, spinal cord and peripheral nerves. Rarely, polymyositis and myoglobinuria are seen. Two other neuromuscular syndromes in people with HIV antibodies are nemaline myopathy and bibrachial amyotrophic diplegia, a form of motor neuron disease. The associations between these diseases and the possibility that HIV infection could be a risk factor for either amyotrophic lateral sclerosis (ALS) itself or other motor neuron diseases are investigated. PMID:21842590

  16. Does quadriceps neuromuscular activation capability explain walking speed in older men and women?

    PubMed

    Clark, David J; Reid, Kieran F; Patten, Carolynn; Phillips, Edward M; Ring, Sarah A; Wu, Samuel S; Fielding, Roger A

    2014-07-01

    Age-related impairment of neuromuscular activation has been shown to contribute to weakness in older adults. However, it is unclear to what extent impaired neuromuscular activation independently accounts for decline of mobility function. The hypothesis of this study is that the capability to produce rapid neuromuscular activation during maximal effort leg muscle contractions will be shown to be an independent predictor of mobility function in older men and women after accounting for muscle size and adiposity, body composition and age. Twenty six older men and eighteen older women (aged 70-85years) participated in this study. Mobility function was assessed by the 400-m walk test. Neuromuscular activation of the quadriceps muscle group was assessed by surface electromyography ("rate of EMG rise"). Thigh muscle cross sectional area and adiposity were assessed by computed tomography. In males, univariate regression analysis revealed strong associations between walking speed and a number of predictors including age (p<0.01), muscle area (p<0.01), intermuscular adipose tissue area (p<0.01), and rate of EMG rise (p<0.001). Subsequent multiple regression analysis with all variables accounted for 72% of the variability in walking speed (p<.0001), with age and rate of EMG rise as the dominant variables in the model. In females, univariate analysis showed a significant association only between walking speed and subcutaneous adipose tissue area (p<0.05). Multiple regression analysis accounted for only 44% of the variability in walking speed, and was not statistically significant (p=0.18). The present findings indicate that the capability to rapidly activate the quadriceps muscle group is an important factor accounting for inter-individual variability of walking speed among older men, but not among older women. This research is important for informing the design of assessments and interventions that seek to detect and prevent impairments that contribute to age-related mobility

  17. Effects of in vivo injury on the neuromuscular junction in healthy and dystrophic muscles

    PubMed Central

    Pratt, Stephen JP; Shah, Sameer B; Ward, Christopher W; Inacio, Mario P; Stains, Joseph P; Lovering, Richard M

    2013-01-01

    The most common and severe form of muscular dystrophy is Duchenne muscular dystrophy (DMD), a disorder caused by the absence of dystrophin, a structural protein found on the cytoplasmic surface of the sarcolemma of striated muscle fibres. Considerable attention has been dedicated to studying myofibre damage and muscle plasticity, but there is little information to determine if damage from contraction-induced injury occurs at or near the nerve terminal axon. We used α-bungarotoxin to compare neuromuscular junction (NMJ) morphology in healthy (wild-type, WT) and dystrophic (mdx) mouse quadriceps muscles and evaluated transcript levels of the post-synaptic muscle-specific kinase signalling complex. Our focus was to study changes in NMJs after injury induced with an established in vivo animal injury model. Neuromuscular transmission, electromyography (EMG), and NMJ morphology were assessed 24 h after injury. In non-injured muscle, muscle-specific kinase expression was significantly decreased in mdx compared to WT. Injury resulted in a significant loss of maximal torque in WT (39 ± 6%) and mdx (76 ± 8%) quadriceps, but significant changes in NMJ morphology, neuromuscular transmission and EMG data were found only in mdx following injury. Compared with WT mice, motor end-plates of mdx mice demonstrated less continuous morphology, more disperse acetylcholine receptor aggregates and increased number of individual acetylcholine receptor clusters, an effect that was exacerbated following injury. Neuromuscular transmission failure increased and the EMG measures decreased after injury in mdx mice only. The data show that eccentric contraction-induced injury causes morphological and functional changes to the NMJs in mdx skeletal muscle, which may play a role in excitation–contraction coupling failure and progression of the dystrophic process. PMID:23109110

  18. Cough augmentation with mechanical insufflation/exsufflation in patients with neuromuscular weakness.

    PubMed

    Chatwin, M; Ross, E; Hart, N; Nickol, A H; Polkey, M I; Simonds, A K

    2003-03-01

    Adults and children with neuromuscular disease exhibit weak cough and are susceptible to recurrent chest infections, a major cause of morbidity and mortality. Mechanical insufflation/exsufflation may improve cough efficacy by increasing peak cough flow. It was hypothesised that mechanical insufflation/exsufflation would produce a greater increase in peak cough flow than other modes of cough augmentation. The acceptability of these interventions was also compared. Twenty-two patients aged 10-56 yrs (median 21 yrs) with neuromuscular disease and 19 age-matched controls were studied. Spirometry was performed and respiratory muscle strength measured. Peak cough flow was recorded during maximal unassisted coughs, followed in random order by coughs assisted by physiotherapy, noninvasive ventilation, insufflation and exsufflation, and exsufflation alone. Subjects rated strength of cough, distress and comfort on a visual analogue scale. In the neuromuscular disease group, mean +/- SD forced expiratory volume in one second was 0.8 +/- 0.6 L x s(-1), forced vital capacity 0.9 +/- 0.8 L, maximum inspiratory pressure 25 +/- 16 cmH2O, maximum expiratory pressure 26 +/- 22 cmH2O and unassisted peak cough flow 169 +/- 90 L x min(-1). The greatest increase in peak cough flow was observed with mechanical insufflation/exsufflation at 235 +/- 111 L x min(-1) (p<0.01). All techniques showed similar patient acceptability. Mechanical insufflation/exsufflation produces a greater increase in peak cough flow than other standard cough augmentation techniques in adults and children with neuromuscular disease.

  19. Fermion-scalar conformal blocks

    DOE PAGES

    Iliesiu, Luca; Kos, Filip; Poland, David; Pufu, Silviu S.; Simmons-Duffin, David; Yacoby, Ran

    2016-04-13

    In this study, we compute the conformal blocks associated with scalar-scalar-fermionfermion 4-point functions in 3D CFTs. Together with the known scalar conformal blocks, our result completes the task of determining the so-called ‘seed blocks’ in three dimensions. In addition, conformal blocks associated with 4-point functions of operators with arbitrary spins can now be determined from these seed blocks by using known differential operators.

  20. Porous block nanofiber composite filters

    DOEpatents

    Ginley, David S.; Curtis, Calvin J.; Miedaner, Alexander; Weiss, Alan J.; Paddock, Arnold

    2016-08-09

    Porous block nano-fiber composite (110), a filtration system (10) and methods of using the same are disclosed. An exemplary porous block nano-fiber composite (110) includes a porous block (100) having one or more pores (200). The porous block nano-fiber composite (110) also includes a plurality of inorganic nano-fibers (211) formed within at least one of the pores (200).

  1. Comparison of electromyography and kinemyography during recovery from non-depolarising neuromuscular blockade.

    PubMed

    Stewart, P A; Freelander, N; Liang, S; Heller, G; Phillips, S

    2014-05-01

    In this study, two commercially available quantitative neuromuscular function monitoring techniques, electromyography (EMG) and kinemyography (KMG), were compared with respect to repeatability and accuracy during late recovery from neuromuscular blockade. Train-of-four (TOF) ratios were recorded in 30 patients using KMG and EMG at the adductor pollicis muscle. Measurements were taken on the same hand using the Datex-Ohmeda NeuroMuscular Transmission monitor (GE Healthcare, Helsinki, Finland). Instrumental precision was evaluated using the coefficient of repeatability, while accuracy was assessed using the bias and limits of agreement. The coefficients of repeatability were similar for both techniques (0.035 for KMG and 0.043 for EMG), indicating a similar level of precision. KMG overestimated the TOF ratios measured with EMG with a bias of 0.11 (95% limits of agreement: -0.13 to 0.35). At a TOF ratio of 0.90 the bias was 0.08 (95% limits of agreement: -0.08 to 0.25). This means that at a TOF ratio of 0.90 measured with KMG will be approximately equivalent to a TOF ratio of 0.80 measured with EMG at the adductor pollicis muscle, but it may indeed be as low as 0.65 or as high as 1.00. Therefore, TOF ratios measured by KMG and EMG cannot be used interchangeably.

  2. Physiological control of elaborate male courtship: Female choice for neuromuscular systems

    PubMed Central

    Fusani, Leonida; Barske, Julia; Day, Lainy D.; Fuxjager, Matthew J.; Schlinger, Barney A.

    2015-01-01

    Males of many animal species perform specialized courtship behaviours to gain copulations with females. Identifying physiological and anatomical specializations underlying performance of these behaviours helps clarify mechanisms through which sexual selection promotes the evolution of elaborate courtship. Our knowledge about neuromuscular specializations that support elaborate displays is limited to a few model species. In this review, we focus on the physiological control of the courtship of a tropical bird, the golden-collared manakin, which has been the focus of our research for nearly 20 years. Male manakins perform physically elaborate courtship displays that are quick, accurate and powerful. Females seem to choose males based on their motor skills suggesting that neuromuscular specializations possessed by these males are driven by female choice. Male courtship is activated by androgens and androgen receptors are expressed in qualitatively and quantitatively unconventional ways in manakin brain, spinal cord and skeletal muscles. We propose that in some species, females select males based on their neuromuscular capabilities and acquired skills and that elaborate steroid-dependent courtship displays evolve to signal these traits. PMID:25086380

  3. Physiological control of elaborate male courtship: female choice for neuromuscular systems.

    PubMed

    Fusani, Leonida; Barske, Julia; Day, Lainy D; Fuxjager, Matthew J; Schlinger, Barney A

    2014-10-01

    Males of many animal species perform specialized courtship behaviours to gain copulations with females. Identifying physiological and anatomical specializations underlying performance of these behaviours helps clarify mechanisms through which sexual selection promotes the evolution of elaborate courtship. Our knowledge about neuromuscular specializations that support elaborate displays is limited to a few model species. In this review, we focus on the physiological control of the courtship of a tropical bird, the golden-collared manakin, which has been the focus of our research for nearly 20 years. Male manakins perform physically elaborate courtship displays that are quick, accurate and powerful. Females seem to choose males based on their motor skills suggesting that neuromuscular specializations possessed by these males are driven by female choice. Male courtship is activated by androgens and androgen receptors are expressed in qualitatively and quantitatively unconventional ways in manakin brain, spinal cord and skeletal muscles. We propose that in some species, females select males based on their neuromuscular capabilities and acquired skills and that elaborate steroid-dependent courtship displays evolve to signal these traits. PMID:25086380

  4. Neuromuscular onset succession of high level gymnasts during dynamic leg acceleration phases on high bar.

    PubMed

    von Laßberg, Christoph; Rapp, Walter; Mohler, Betty; Krug, Jürgen

    2013-10-01

    In several athletic disciplines there is evidence that for generating the most effective acceleration of a specific body part the transfer of momentum should run in a "whip-like" consecutive succession of body parts towards the segment which shall be accelerated most effectively (e.g. the arm in throwing disciplines). This study investigated the question how this relates to the succession of neuromuscular activation to induce such "whip like" leg acceleration in sports like gymnastics with changed conditions concerning the body position and momentary rotational axis of movements (e.g. performing giant swings on high bar). The study demonstrates that during different long hang elements, performed by 12 high level gymnasts, the succession of the neuromuscular activation runs primarily from the bar (punctum fixum) towards the legs (punctum mobile). This demonstrates that the frequently used teaching instruction, first to accelerate the legs for a successful realization of such movements, according to a high level kinematic output, is contradictory to the neuromuscular input patterns, being used in high level athletes, realizing these skills with high efficiency. Based on these findings new approaches could be developed for more direct and more adequate teaching methods regarding to an earlier optimization and facilitation of fundamental movement requirements.

  5. Minimally Invasive Scoliosis Surgery: A Novel Technique in Patients with Neuromuscular Scoliosis

    PubMed Central

    Sarwahi, Vishal; Amaral, Terry; Wendolowski, Stephen; Gecelter, Rachel; Gambassi, Melanie; Plakas, Christos; Liao, Benita; Kalantre, Sarika; Katyal, Chhavi

    2015-01-01

    Minimally invasive surgery (MIS) has been described in the treatment of adolescent idiopathic scoliosis (AIS) and adult scoliosis. The advantages of this approach include less blood loss, shorter hospital stay, earlier mobilization, less tissue disruption, and relatively less pain. However, despite these significant benefits, MIS approach has not been reported in neuromuscular scoliosis patients. This is possibly due to concerns with longer surgery time, which is further increased due to more levels fused and instrumented, challenges of pelvic fixation, size and number of incisions, and prolonged anesthesia. We modified the MIS approach utilized in our AIS patients to be implemented in our neuromuscular patients. Our technique allows easy passage of contoured rods, placement of pedicle screws without image guidance, partial/complete facet resection, and all standard reduction maneuvers. Operative time needed to complete this surgery is comparable to the standard procedure and the majority of our patients have been extubated at the end of procedure, spending 1 day in the PICU and 5-6 days in the hospital. We feel that MIS is not only a feasible but also a superior option in patients with neuromuscular scoliosis. Long-term results are unavailable; however, short-term results have shown multiple benefits of this approach and fewer limitations. PMID:26649305

  6. Comparison of the Capacity of Different Jump and Sprint Field Tests to Detect Neuromuscular Fatigue.

    PubMed

    Gathercole, Rob J; Sporer, Ben C; Stellingwerff, Trent; Sleivert, Gord G

    2015-09-01

    Different jump and sprint tests have been used to assess neuromuscular fatigue, but the test with optimal validity remains to be established. The current investigation examined the suitability of vertical jump (countermovement jump [CMJ], squat jump [SJ], drop jump [DJ]) and 20-m sprint (SPRINT) testing for neuromuscular fatigue detection. On 6 separate occasions, 11 male team-sport athletes performed 6 CMJ, SJ, DJ, and 3 SPRINT trials. Repeatability was determined on the first 3 visits, with subsequent 3 visits (0-, 24-, and 72-hour postexercise) following a fatiguing Yo-Yo running protocol. SPRINT performance was most repeatable (mean coefficient of variation ≤2%), whereas DJ testing (4.8%) was significantly less repeatable than CMJ (3.0%) and SJ (3.5%). Each test displayed large decreases at 0-hour (33 of 49 total variables; mean effect size = 1.82), with fewer and smaller decreases at 24-hour postexercise (13 variables; 0.75), and 72-hour postexercise (19 variables; 0.78). SPRINT displayed the largest decreases at 0-hour (3.65) but was subsequently unchanged, whereas SJ performance recovered by 72-hour postexercise. In contrast, CMJ and DJ performance displayed moderate (12 variables; 1.18) and small (6 variables; 0.53) reductions at 72-hour postexercise, respectively. Consequently, the high repeatability and immediate and prolonged fatigue-induced changes indicated CMJ testing as most suitable for neuromuscular fatigue monitoring. PMID:26308829

  7. The effects of whirlpool bath and neuromuscular electrical stimulation on complex regional pain syndrome.

    PubMed

    Devrimsel, Gul; Turkyilmaz, Aysegul Kucukali; Yildirim, Murat; Beyazal, Munevver Serdaroglu

    2015-01-01

    [Purpose] The aim of the present study was to investigate and compare the effects of whirlpool bath and neuromuscular electrical stimulation on complex regional pain syndrome. [Subjects and Methods] Sixty outpatients (30 per group) with complex regional pain syndrome participated. They received 15 treatment 5 days per week for 3 weeks. The outcome measures were the visual analogue scale for pain, edema, range of motion of the wrist (flexion and extension), fingertip-to-distal palmar crease distance, hand grip strength, and pinch strength. All parameters were measured at baseline (week 0) and at the trial end (week 3). [Results] There were significant improvements in all parameters after therapy in both groups. The whirlpool bath group showed significantly better improvements in the visual analogue score, hand edema, hand grip strength, wrist range of motion (both flexion and extension), fingertip-to-distal palmar crease distance, and the three-point and fingertip pinch strengths than the neuromuscular electrical stimulation group; however, the lateral pinch strengths were similar. [Conclusion] Both whirlpool bath and neuromuscular electrical stimulation are effective in the treatment of complex regional pain syndrome, but the efficacy of the whirlpool bath treatment was better.

  8. Neuromuscular fatigue recovery following rapid and slow stretch-shortening cycle movements.

    PubMed

    Wadden, Katie P; Button, Duane C; Kibele, Armin; Behm, David G

    2012-06-01

    The purpose of this study was to investigate underlying mechanisms and neuromuscular recovery patterns following rapid and slow stretch-shortening cycle (SSC) movements performed to fatigue. Fourteen (10 moderately trained (MT) and four highly trained (HT)) subjects completed rapid and slow SSC movements to fatigue. The rapid SSC movement consisted of continuous drop jumps from a 30 cm platform until a predetermined jump height was no longer maintained, and the slow SSC movement consisted of continuous squats to 90° of knee flexion at a load of 65% of subject's one-repetition maximum until no further repetitions could be completed. Although blood lactate measures were significantly (p < 0.002) higher after the rapid SSC condition versus after the slow SSC condition, the recovery of neuromuscular properties (maximum voluntary contractions, twitch force, muscle compound action potential) following the two conditions to fatigue did not differ. The duration of the rapid SSC movement was dependent on the training status of the subject; HT subjects performed the rapid SSC longer (68.2%) than the MT subjects until fatigued. Thus, the neuromuscular fatigue recovery patterns were independent of the type of SSC movement, condition duration, and subject training status. Because rapid and slow SSC exercises induce similar fatigue patterns, training programs incorporating rapid SSC exercises can be developed similar to that prescribed in traditional slow SSC resistance training programs.

  9. Increased quantal release of acetylcholine at the neuromuscular junction following scald injury in the rat.

    PubMed

    Edwards, J P; Hatton, P A; Little, R A; Pennington, R A; Wareham, A C

    1999-12-01

    Following severe burns, patients frequently develop a profound resistance to nondepolarizing neuromuscular blockers. Several mechanisms have been proposed to account for this, including upregulation of nicotinic acetylcholine receptors. We investigated the effects of a 30% body surface area (BSA) scald on neuromuscular transmission in slow-twitch soleus (SOL) and fast-twitch extensor digitorum longus (EDL) of rats. Rats were sacrificed 72 h after the injury, a time at which sepsis is unlikely and body weight gain and core temperature have returned to normal. Further groups of rats were sham operated and either pair fed to the scalded rats or freely fed to assess the influence of food restriction. When compared with muscle from pair-fed control rats, scald resulted in an almost 50% increase in miniature endplate potential (mEPP) frequency in both SOL and EDL. However, scald did not increase mean mEPP amplitude in SOL, although it did cause a 10% increase in EDL. Scald injury did produce a significant increase in the size of the evoked endplate potential in SOL (33%) and EDL (37%). These data indicate that a significant increase in the quantal content of evoked transmitter released in SOL (38%) and EDL (30%) occurred by 72 h after scald. Such an increase may contribute to the resistance to nondepolarizing neuromuscular blockers documented in patients following thermal injury.

  10. Telemedicine system for the care of patients with neuromuscular disease and chronic respiratory failure

    PubMed Central

    Morete, Emilio; González, Francisco

    2014-01-01

    Introduction Neuromuscular diseases cause a number of limitations which may be improved by using a telemedicine system. These include functional impairment and dependence associated with muscle weakness, the insidious development of respiratory failure and episodes of exacerbation. Material and methods The present study involved three patients with severe neuromuscular disease, chronic respiratory failure and long-term mechanical ventilation, who were followed up using a telemedicine platform. The telemedicine system is based on videoconferencing and telemonitoring of cardiorespiratory variables (oxygen saturation, heart rate, blood pressure and electrocardiogram). Two different protocols were followed depending on whether the patient condition was stable or unstable. Results Over a period of 5 years, we analyzed a series of variables including use of the system, patient satisfaction and clinical impact. Overall we performed 290 videoconference sessions, 269 short monitoring oximetry measurements and 110 blood pressure measurements. With respect to the clinical impact, after enrolment in the telemedicine program, the total number of hospital admissions fell from 18 to 3. Conclusions Our findings indicate that the system was user friendly for patients and care givers. Patient satisfaction scores were acceptable. The telemedicine system was effective for the home treatment of three patients with severe neuromuscular diseases and reduced the need for hospital admissions. PMID:25395959

  11. Quantitative neuromuscular ultrasound in intensive care unit-acquired weakness: A systematic review.

    PubMed

    Bunnell, Aaron; Ney, John; Gellhorn, Alfred; Hough, Catherine L

    2015-11-01

    Intensive care unit-acquired weakness (ICU-AW) causes significant morbidity and impairment in critically ill patients. Recent advances in neuromuscular ultrasound (NMUS) allow evaluation of neuromuscular pathology early in critical illness. Here we review application of ultrasound in ICU-AW. MEDLINE-indexed articles were searched for terms relevant to ultrasound and critical illness. Two reviewers evaluated the resulting abstracts (n = 218) and completed full-text review (n = 13). Twelve studies and 1 case report were included. Ten studies evaluated muscle thickness or cross-sectional area (CSA): 8 reported a decrease, and 2 reported no change. Two studies reported preservation of muscle thickness in response to neuromuscular electrical stimulation, and 1 found no preservation. One study found decreases in gray-scale standard deviation, but no change in echogenicity. One study described increases in echogenicity and fasciculations. Ultrasound reliability in ICU-AW is not fully established. Further investigation is needed to identify ultrasound measures that reliably predict clinical, electrodiagnostic, and pathologic findings of ICU-AW.

  12. Lumbar hyperlordosis of neuromuscular origin: pathophysiology and surgical strategy for correction

    PubMed Central

    Khouri, Nejib; Glorion, Christophe; Lechevallier, Joël; Morin, Christian

    2006-01-01

    Lumbar hyperlordosis of neuromuscular origin is rare and requires surgical treatment in order to preserve a good sitting posture. We report twenty-seven cases of a preponderantly sagittal hyperlordosis deformity of the lumbar spine in patients with neuromuscular disorders and identify the indications and results of treatment. Seventeen males and ten females, aged 13 to 27 years, underwent operations for a lumbar hyperlordosis of neuromuscular origin responsible for major difficulties in sitting. In all patients, the sacrum was horizontal and associated in twenty-six cases with marked pelvic anteversion. Eleven patients were treated surgically by a posterior approach. The sixteen remaining patients had a preliminary discectomy, followed by posterior correction and fusion. Lumbar hyperlordosis was reduced from 8° to 77° between L1 and S1. The horizontal sacrum was partially reduced with an improvement from 8° to 50°. Consequently, patients recovered a comfortable sitting position. One patient died of respiratory complications six weeks after surgery. Surgical correction is a demanding procedure which can be performed by a posterior approach. It is mandatory to analyse the spino-pelvic balance to avoid iliac retroversion and the loss of the role of the ischia in the sitting position. PMID:16967278

  13. Loss of Glial Neurofascin155 Delays Developmental Synapse Elimination at the Neuromuscular Junction

    PubMed Central

    Roche, Sarah L.; Sherman, Diane L.; Dissanayake, Kosala; Soucy, Geneviève; Desmazieres, Anne; Lamont, Douglas J.; Peles, Elior; Julien, Jean-Pierre; Wishart, Thomas M.; Ribchester, Richard R.; Brophy, Peter J.

    2014-01-01

    Postnatal synapse elimination plays a critical role in sculpting and refining neural connectivity throughout the central and peripheral nervous systems, including the removal of supernumerary axonal inputs from neuromuscular junctions (NMJs). Here, we reveal a novel and important role for myelinating glia in regulating synapse elimination at the mouse NMJ, where loss of a single glial cell protein, the glial isoform of neurofascin (Nfasc155), was sufficient to disrupt postnatal remodeling of synaptic circuitry. Neuromuscular synapses were formed normally in mice lacking Nfasc155, including the establishment of robust neuromuscular synaptic transmission. However, loss of Nfasc155 was sufficient to cause a robust delay in postnatal synapse elimination at the NMJ across all muscle groups examined. Nfasc155 regulated neuronal remodeling independently of its canonical role in forming paranodal axo–glial junctions, as synapse elimination occurred normally in mice lacking the axonal paranodal protein Caspr. Rather, high-resolution proteomic screens revealed that loss of Nfasc155 from glial cells was sufficient to disrupt neuronal cytoskeletal organization and trafficking pathways, resulting in reduced levels of neurofilament light (NF-L) protein in distal axons and motor nerve terminals. Mice lacking NF-L recapitulated the delayed synapse elimination phenotype observed in mice lacking Nfasc155, suggesting that glial cells regulate synapse elimination, at least in part, through modulation of the axonal cytoskeleton. Together, our study reveals a glial cell-dependent pathway regulating the sculpting of neuronal connectivity and synaptic circuitry in the peripheral nervous system. PMID:25232125

  14. Loss of glial neurofascin155 delays developmental synapse elimination at the neuromuscular junction.

    PubMed

    Roche, Sarah L; Sherman, Diane L; Dissanayake, Kosala; Soucy, Geneviève; Desmazieres, Anne; Lamont, Douglas J; Peles, Elior; Julien, Jean-Pierre; Wishart, Thomas M; Ribchester, Richard R; Brophy, Peter J; Gillingwater, Thomas H

    2014-09-17

    Postnatal synapse elimination plays a critical role in sculpting and refining neural connectivity throughout the central and peripheral nervous systems, including the removal of supernumerary axonal inputs from neuromuscular junctions (NMJs). Here, we reveal a novel and important role for myelinating glia in regulating synapse elimination at the mouse NMJ, where loss of a single glial cell protein, the glial isoform of neurofascin (Nfasc155), was sufficient to disrupt postnatal remodeling of synaptic circuitry. Neuromuscular synapses were formed normally in mice lacking Nfasc155, including the establishment of robust neuromuscular synaptic transmission. However, loss of Nfasc155 was sufficient to cause a robust delay in postnatal synapse elimination at the NMJ across all muscle groups examined. Nfasc155 regulated neuronal remodeling independently of its canonical role in forming paranodal axo-glial junctions, as synapse elimination occurred normally in mice lacking the axonal paranodal protein Caspr. Rather, high-resolution proteomic screens revealed that loss of Nfasc155 from glial cells was sufficient to disrupt neuronal cytoskeletal organization and trafficking pathways, resulting in reduced levels of neurofilament light (NF-L) protein in distal axons and motor nerve terminals. Mice lacking NF-L recapitulated the delayed synapse elimination phenotype observed in mice lacking Nfasc155, suggesting that glial cells regulate synapse elimination, at least in part, through modulation of the axonal cytoskeleton. Together, our study reveals a glial cell-dependent pathway regulating the sculpting of neuronal connectivity and synaptic circuitry in the peripheral nervous system. PMID:25232125

  15. Comparison of the Capacity of Different Jump and Sprint Field Tests to Detect Neuromuscular Fatigue.

    PubMed

    Gathercole, Rob J; Sporer, Ben C; Stellingwerff, Trent; Sleivert, Gord G

    2015-09-01

    Different jump and sprint tests have been used to assess neuromuscular fatigue, but the test with optimal validity remains to be established. The current investigation examined the suitability of vertical jump (countermovement jump [CMJ], squat jump [SJ], drop jump [DJ]) and 20-m sprint (SPRINT) testing for neuromuscular fatigue detection. On 6 separate occasions, 11 male team-sport athletes performed 6 CMJ, SJ, DJ, and 3 SPRINT trials. Repeatability was determined on the first 3 visits, with subsequent 3 visits (0-, 24-, and 72-hour postexercise) following a fatiguing Yo-Yo running protocol. SPRINT performance was most repeatable (mean coefficient of variation ≤2%), whereas DJ testing (4.8%) was significantly less repeatable than CMJ (3.0%) and SJ (3.5%). Each test displayed large decreases at 0-hour (33 of 49 total variables; mean effect size = 1.82), with fewer and smaller decreases at 24-hour postexercise (13 variables; 0.75), and 72-hour postexercise (19 variables; 0.78). SPRINT displayed the largest decreases at 0-hour (3.65) but was subsequently unchanged, whereas SJ performance recovered by 72-hour postexercise. In contrast, CMJ and DJ performance displayed moderate (12 variables; 1.18) and small (6 variables; 0.53) reductions at 72-hour postexercise, respectively. Consequently, the high repeatability and immediate and prolonged fatigue-induced changes indicated CMJ testing as most suitable for neuromuscular fatigue monitoring.

  16. Comparing targeted exome and whole exome approaches for genetic diagnosis of neuromuscular disorders

    PubMed Central

    Gorokhova, Svetlana; Cerino, Mathieu; Mathieu, Yves; Courrier, Sébastien; Desvignes, Jean-Pierre; Salgado, David; Béroud, Christophe; Krahn, Martin; Bartoli, Marc

    2015-01-01

    Massively parallel sequencing is rapidly becoming a widely used method in genetic diagnostics. However, there is still no clear consensus as to which approach can most efficiently identify the pathogenic mutations carried by a given patient, while avoiding false negative and false positive results. We developed a targeted exome approach (MyoPanel2) in order to optimize genetic diagnosis of neuromuscular disorders. Using this approach, we were able to analyse 306 genes known to be mutated in myopathies as well as in related disorders, obtaining 98.8% target sequence coverage at 20 ×. Moreover, MyoPanel2 was able to detect 99.7% of 11,467 known mutations responsible for neuromuscular disorders. We have then used several quality control parameters to compare performance of the targeted exome approach with that of whole exome sequencing. The results of this pilot study of 140 DNA samples suggest that targeted exome sequencing approach is an efficient genetic diagnostic test for most neuromuscular diseases. PMID:27054082

  17. Role of extracellular matrix proteins and their receptors in the development of the vertebrate neuromuscular junction.

    PubMed

    Singhal, Neha; Martin, Paul T

    2011-11-01

    The vertebrate neuromuscular junction (NMJ) remains the best-studied model for understanding the mechanisms involved in synaptogenesis, due to its relatively large size, its simplicity of patterning, and its unparalleled experimental accessibility. During neuromuscular development, each skeletal myofiber secretes and deposits around its extracellular surface an assemblage of extracellular matrix (ECM) proteins that ultimately form a basal lamina. This is also the case at the NMJ, where the motor nerve contributes additional factors. Before most of the current molecular components were known, it was clear that the synaptic ECM of adult skeletal muscles was unique in composition and contained factors sufficient to induce the differentiation of both pre- and postsynaptic membranes. Biochemical, genetic, and microscopy studies have confirmed that agrin, laminin (221, 421, and 521), collagen IV (α3-α6), collagen XIII, perlecan, and the ColQ-bound form of acetylcholinesterase are all synaptic ECM proteins with important roles in neuromuscular development. The roles of their many potential receptors and/or binding proteins have been more difficult to assess at the genetic level due to the complexity of membrane interactions with these large proteins, but roles for MuSK-LRP4 in agrin signaling and for integrins, dystroglycan, and voltage-gated calcium channels in laminin-dependent phenotypes have been identified. Synaptic ECM proteins and their receptors are involved in almost all aspects of synaptic development, including synaptic initiation, topography, ultrastructure, maturation, stability, and transmission. PMID:21766463

  18. The Knockdown of αkap Alters the Postsynaptic Apparatus of Neuromuscular Junctions in Living Mice

    PubMed Central

    Martinez-Pena y Valenzuela, Isabel; Aittaleb, Mohamed; Chen, Po-Ju

    2015-01-01

    A muscle-specific nonkinase anchoring protein (αkap), encoded within the calcium/calmodulin kinase II (camk2) α gene, was recently found to control the stability of acetylcholine receptor (AChR) clusters on the surface of cultured myotubes. However, it remains unknown whether this protein has any effect on receptor stability and the maintenance of the structural integrity of neuromuscular synapses in vivo. By knocking down the endogenous expression of αkap in mouse sternomastoid muscles with shRNA, we found that the postsynaptic receptor density was dramatically reduced, the turnover rate of receptors at synaptic sites was significantly increased, and the insertion rates of both newly synthesized and recycled receptors into the postsynaptic membrane were depressed. Moreover, we found that αkap shRNA knockdown impaired synaptic structure as postsynaptic AChR clusters and their associated postsynaptic scaffold proteins within the neuromuscular junction were completely eliminated. These results provide new mechanistic insight into the role of αkap in regulating the stability of the postsynaptic apparatus of neuromuscular synapses. PMID:25834039

  19. Requirement of enhanced Survival Motoneuron protein imposed during neuromuscular junction maturation

    PubMed Central

    Kariya, Shingo; Obis, Teresa; Garone, Caterina; Akay, Turgay; Sera, Fusako; Iwata, Shinichi; Homma, Shunichi; Monani, Umrao R.

    2014-01-01

    Spinal muscular atrophy is a common motor neuron disease caused by low survival motoneuron (SMN), a key protein in the proper splicing of genes. Restoring the protein is therefore a promising therapeutic strategy. Implementation of this strategy, however, depends on defining the temporal requirements for SMN. Here, we used controlled knockdown of SMN in transgenic mice to determine the precise postnatal stage requirements for this protein. Reducing SMN in neonatal mice resulted in a classic SMA-like phenotype. Unexpectedly, depletion of SMN in adults had relatively little effect. Insensitivity to low SMN emerged abruptly at postnatal day 17, which coincided with establishment of the fully mature neuromuscular junction (NMJ). Mature animals depleted of SMN eventually exhibited evidence of selective neuromuscular pathology that was made worse by traumatic injury. The ability to regenerate the mature NMJ in aged or injured SMN-depleted mice was grossly impaired, a likely consequence of the inability to meet the surge in demand for motoneuronal SMN that was seen in controls. Our results demonstrate that relative maturity of the NMJ determines the temporal requirement for the SMN protein. These observations suggest that the use of potent but potentially deleterious SMN-enhancing agents could be tapered in human patients once the neuromuscular system matures and reintroduced as needed to enhance SMN for remodeling aged or injured NMJs. PMID:24463453

  20. Variation in neuromuscular activity during prey capture by trophic specialists and generalists (Pisces: Labridae).

    PubMed

    Sanderson, S L

    1988-01-01

    Members of the marine teleost family Labridae are among the most abundant and morphologically diverse fish on coral reefs. A quantitative analysis was conducted of the neuromuscular activity patterns controlling movement of the jaws during prey capture by 4 labrid species ranging from trophic specialists to trophic generalists. A total of more than 800 captures of 3 prey types was analyzed. All 4 species showed significant modulation of electromyographic parameters in response to different prey types. Significant variation was also found between replicate experiments on the same individuals. To obtain valid assessments of interspecific variability, statistical analyses must take into account this potentially high degree of intraspecific variability. By partitioning the variance in a nested analysis of variance, a lack of significant differences in electromyographic parameters between species became apparent. In contrast to the closely related Cichlidae, trophic diversification in the Labridae has not been accompanied by the acquisition of unique neuromuscular activity patterns for prey capture. The dramatic adaptive radiation that has occurred in these 2 families has involved different processes of evolutionary diversification. Neuromuscular stereotypy of labrids may be associated with the lack of structural flexibility in their 'coupled jaw'. Additional study is needed to establish the extent to which labrid radiation into various trophic niches is related to the evolution of specialized morphologies and foraging behaviors.